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Project Title:  Bone Recovery Potential After Bisphosphonate and PTH Treatment of Disuse Osteoporosis Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2004  
End Date: 05/31/2008  
Task Last Updated: 10/08/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Schaffler, Mitchell B. Ph.D. / Mount Sinai School of Medicine 
Address:  One Gustave L. Levy Place 
Box 1188 
New York , NY 10029-6500 
Email: Mitchell.Schaffler@mssm.edu 
Phone: 212-241-1625  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mount Sinai School of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jepsen, Karl  Mount Sinai School of Medicine 
Majeska, Robert  Mount Sinai School of Medicine 
Project Information: Grant/Contract No. NCC 9-58-BL00406 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NCC 9-58-BL00406 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) B03:What pharmaceuticals against bone loss are best used and how? (merged into Osteo 7) (IRP Rev D)
Task Description: Bone loss in microgravity and the resulting bone fragility have been identified by NASA as key barriers to successful long-term space flight. Effective countermeasures must therefore prevent bone loss, but also to maintain the mechanical integrity of the tissue during prolonged space flight and allow rapid recovery of normal function.

Disuse osteoporosis in humans and higher mammals results from elevated bone resorption. Thus, targeting osteoclasts with antiresorptive agents like bisphosphonate to prevent bone loss is a key strategy. While anti-resorptive drugs have been the cornerstones of osteoporosis therapy, anabolic agents, such as PTH, that stimulate bone formation represent an important new advance in the treatment of osteoporosis. We hypothesize that PTH may be especially valuable in reversing disuse if the deterioration of bone architecture can be slowed such that the anabolic agent has a better initial bone scaffold on which to work.

The studies examine whether bone that remains after bisphosphonate-treatment during long-term immobilization can recover its architecture and mechanical function after restoration of mechanical usage (remobilization). We will then assess whether addition of anabolic PTH during immobilization will improve recovery of disuse bone. Recovery after long-term disuse with bisphosphonate treatment will be examined in an immobilization model. MicroCT imaging will be used to evaluate microstructure, biomechanical testing to assess function and histomorphometry to measure tissue physiological responses.

Research Impact/Earth Benefits: The current research applies directly to prevention and treatment of osteoporosis on Earth. In particular, these studies will examine 1) the efficacy of antiresorptive therapy in slowing the bone loss that occurs with decreased of mechanical loading, and 2) the role of the bone anabolic agent, PTH, in accelerating bone recovery and restoring bone strength. This research uses pharmacological agents that are already approved for clinical use; thus the findings from this research can be expected to see rapid implementation in bone loss situations occurring as a result of unloading, such as spinal cord injury and long-term immobilzation.

Task Progress & Bibliography Information FY2008 
Task Progress: Experiments and analyses are completed. Manuscripts in preparation.

Bibliography Type: Description: (Last Updated: 08/21/2020)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Fritton JC, Li CY, Zhang X, Roth H, Tommasini SM, Laudier D, Mann R, Schaffler MB. "Bisphosphonate and PTH treatments adversely affect cortical bone adaptation to restored weight-bearing." 54th Annual Meeting of the Orthopaedic Research Society, San Francisco, CA, March 2-5, 2008.

Transactions Orthopaedic Research Society, 2008 Mar;54:970. , Mar-2008

Abstracts for Journals and Proceedings Zhang X, Fritton JC, Li CY, Laudier DM, Mann R, Schaffler MB. "Remobilization recovers cancellous bone mass and risedronate improves microarchitecture after long-term disuse." 54th Annual Meeting of the Orthopaedic Research Society, San Francisco, CA, March 2-5, 2008.

Transactions Orthopaedic Research Society, 2008 Mar;54:342. , Mar-2008

Articles in Peer-reviewed Journals Cardoso L, Schaffler MB. "Changes of elastic constants and anisotropy patterns in trabecular bone during disuse-induced bone loss assessed by poroelastic ultrasound." J Biomech Eng. 2015 Jan;137(1):0110081–9. https://doi.org/10.1115/1.4029179 ; PMID: 25412022; PMCID: PMC4290507 , Jan-2015
Project Title:  Bone Recovery Potential After Bisphosphonate and PTH Treatment of Disuse Osteoporosis Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2004  
End Date: 05/31/2008  
Task Last Updated: 11/13/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Schaffler, Mitchell B. Ph.D. / Mount Sinai School of Medicine 
Address:  One Gustave L. Levy Place 
Box 1188 
New York , NY 10029-6500 
Email: Mitchell.Schaffler@mssm.edu 
Phone: 212-241-1625  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mount Sinai School of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jepsen, Karl  Mount Sinai School of Medicine 
Majeska, Robert  Mount Sinai School of Medicine 
Project Information: Grant/Contract No. NCC 9-58-BL00406 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NCC 9-58-BL00406 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) B03:What pharmaceuticals against bone loss are best used and how? (merged into Osteo 7) (IRP Rev D)
Task Description: Bone loss in microgravity and the resulting bone fragility have been identified by NASA as key barriers to successful long-term space flight. Effective countermeasures must therefore prevent bone loss, but also to maintain the mechanical integrity of the tissue during prolonged space flight and allow rapid recovery of normal function.

Disuse osteoporosis in humans and higher mammals results from elevated bone resorption. Thus, targeting osteoclasts with antiresorptive agents like bisphosphonate to prevent bone loss is a key strategy. While anti-resorptive drugs have been the cornerstones of osteoporosis therapy, anabolic agents, such as PTH, that stimulate bone formation represent an important new advance in the treatment of osteoporosis. We hypothesize that PTH may be especially valuable in reversing disuse if the deterioration of bone architecture can be slowed such that the anabolic agent has a better initial bone scaffold on which to work.

The studies examine whether bone that remains after bisphosphonate-treatment during long-term immobilization can recover its architecture and mechanical function after restoration of mechanical usage (remobilization). We will then assess whether addition of anabolic PTH during immobilization will improve recovery of disuse bone. Recovery after long-term disuse with bisphosphonate treatment will be examined in an immobilization model. MicroCT imaging will be used to evaluate microstructure, biomechanical testing to assess function and histomorphometry to measure tissue physiological responses.

Research Impact/Earth Benefits: The current research applies directly to prevention and treatment of osteoporosis on Earth. In particular, these studies examine 1) the efficacy of antiresorptive therapy in slowing the bone loss that occurs with loss of mechanical loading, and 2) the use of the bone anabolic agent, PTH, to accelerate bone recovery. Since we are working with pharmacological agents that are already approved for clinical use, the findings from this research can be expected to see rapid implementation in bone loss situations occurring as a result of unloading, such as spinal cord injury and long-term immobilization.

Task Progress & Bibliography Information FY2007 
Task Progress: In vivo studies (Immobilization with and without bisphosphonate, followed by restored weight bearing with and without anabolic PTH treatment, total duration 18 month durations) have been completed. MicroCT analysis of all cortical bone samples has been completed, and reveal that bishosphonate antiresorptives may adversely affect bone recover from disuse Analyses of metaphyseal cancellous bone are ongoing, as are bone histomorphometry and biomechanical studies for all sites.

Bibliography Type: Description: (Last Updated: 08/21/2020)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Li CY, Jepsen KJ, Majeska RJ, Zhang J, Ni R, Gelb BD, Schaffler MB. "Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass." J Bone Miner Res. 2006 Jun;21(6):865-75. PMID: 16753017 , Jun-2006
Project Title:  Bone Recovery Potential After Bisphosphonate and PTH Treatment of Disuse Osteoporosis Reduce
Fiscal Year: FY 2006 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2004  
End Date: 05/31/2008  
Task Last Updated: 01/08/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Schaffler, Mitchell B. Ph.D. / Mount Sinai School of Medicine 
Address:  One Gustave L. Levy Place 
Box 1188 
New York , NY 10029-6500 
Email: Mitchell.Schaffler@mssm.edu 
Phone: 212-241-1625  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mount Sinai School of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jepsen, Karl  Mount Sinai School of Medicine 
Majeska, Robert  Mount Sinai School of Medicine 
Project Information: Grant/Contract No. NCC 9-58-BL00406 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NCC 9-58-BL00406 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) B03:What pharmaceuticals against bone loss are best used and how? (merged into Osteo 7) (IRP Rev D)
Task Description: Bone loss in microgravity and the resulting bone fragility have been identified by NASA as key barriers to successful long-term space flight. Effective countermeasures must therefore prevent bone loss, but also to maintain the mechanical integrity of the tissue during prolonged space flight and allow rapid recovery of normal function.

Disuse osteoporosis in humans and higher mammals results from elevated bone resorption. Thus, targeting osteoclasts with antiresorptive agents like bisphosphonate to prevent bone loss is a key strategy. While anti-resorptive drugs have been the cornerstones of osteoporosis therapy, anabolic agents, such as PTH, that stimulate bone formation represent an important new advance in the treatment of osteoporosis. We hypothesize that PTH may be especially valuable in reversing disuse if the deterioration of bone architecture can be slowed such that the anabolic agent has a better initial bone scaffold on which to work.

The studies examine whether bone that remains after bisphosphonate-treatment during long-term immobilization can recover its architecture and mechanical function after restoration of mechanical usage (remobilization). We will then assess whether addition of anabolic PTH during immobilization will improve recovery of disuse bone. Recovery after long-term disuse with bisphosphonate treatment will be examined in an immobilization model. MicroCT imaging will be used to evaluate microstructure, biomechanical testing to assess function and histomorphometry to measure tissue physiological responses.

Research Impact/Earth Benefits: The current research applies directly to prevention and treatment of osteoporosis on Earth. In particular, these studies will examine 1) the efficacy of antiresorptive therapy in slowing the bone loss that occurs with decreased of mechanical loading, and 2) the role of the bone anabolic agent, PTH, in accelerating bone recovery and restoring bone strength. This research uses pharmacological agents that are already approved for clinical use; thus the findings from this research can be expected to see rapid implementation in bone loss situations occurring as a result of unloading, such as spinal cord injury and long-term immobilzation.

Task Progress & Bibliography Information FY2006 
Task Progress: Long-term in vivo studies (Immobilization with and without, followed by restored weight bearing with and without anabolic PTH treatment, total duration 18 month durations) are ongoing and will be completed in late fall, 2006. Analyses of bone architecture, histomorphometry and biomechanics will begin thereafter.

Our studies a structurally-based ultrasound for the prediction of mechanical properties bone are ongoing. Studies on the bone tissues from the current resorption suppression/remobilization + PTH experiments will be performed as these tissues become available.

Bibliography Type: Description: (Last Updated: 08/21/2020)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Li, CY., C. Price, D. A. Laudier, R. J Majeska and M. B. Schaffler "Risedronate treatment only partially preserves cancellous bone mass and microarchitecture after long-term disuse" Jan-2006
Articles in Peer-reviewed Journals McNamara LM, Prendergast PJ, Schaffler MB. "Bone tissue material properties are altered during osteoporosis." J Musculoskelet Neuronal Interact. 2005 Oct-Dec;5(4):342-3. PMID: 16340130 , Oct-2005
Articles in Peer-reviewed Journals Wang L, Wang Y, Han Y, Henderson SC, Majeska RJ, Weinbaum S, Schaffler MB. "In situ measurement of solute transport in the bone lacunar-canalicular system." Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11911-6. PMID: 16087872 , Aug-2005
Project Title:  BONE RECOVERY POTENTIAL AFTER BISPHOSPHONATE AND PTH TREATMENT OF DISUSE OSTEOPOROSIS Reduce
Fiscal Year: FY 2005 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2004  
End Date: 05/31/2008  
Task Last Updated: 10/21/2005 
Download report in PDF pdf
Principal Investigator/Affiliation:   Schaffler, Mitchell B. Ph.D. / Mount Sinai School of Medicine 
Address:  One Gustave L. Levy Place 
Box 1188 
New York , NY 10029-6500 
Email: Mitchell.Schaffler@mssm.edu 
Phone: 212-241-1625  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mount Sinai School of Medicine 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jepsen, Karl  Mount Sinai School of Medicine 
Majeska, Robert  Mount Sinai School of Medicine 
Project Information: Grant/Contract No. NCC 9-58-BL00406 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NCC 9-58-BL00406 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) B03:What pharmaceuticals against bone loss are best used and how? (merged into Osteo 7) (IRP Rev D)
Task Description: Bone loss in microgravity and the resulting bone fragility have been identified by NASA as key barriers to successful long-term space flight. Effective countermeasures must therefore prevent bone loss, but also to maintain the mechanical integrity of the tissue during prolonged space flight and allow rapid recovery of normal function. Disuse osteoporosis in humans and higher mammals results from elevated bone resorption. Thus, targeting osteoclasts with antiresorptive agents like bisphosphonate to prevent bone loss is a key strategy. While anti-resorptive drugs have been the cornerstones of osteoporosis therapy, anabolic agents, such as PTH, that stimulate bone formation represent an important new advance in the treatment of osteoporosis. We hypothesize that PTH may be especially valuable in reversing disuse if the deterioration of bone architecture can be slowed such that the anabolic agent has a better initial bone scaffold on which to work. The studies examine whether bone that remains after bisphosphonate-treatment during long-term immobilization can recover its architecture and mechanical function after restoration of mechanical usage (remobilization). We will then assess whether addition of anabolic PTH during immobilization will improve recovery of disuse bone. Recovery after long-term disuse with bisphosphonate treatment will be examined in an immobilization model. MicroCT imaging will be used to evaluate microstructure, biomechanical testing to assess function and histomorphometry to measure tissue physiological responses.

Research Impact/Earth Benefits: The current research applies directly to prevention and treatment of osteoporosis on Earth. In particular, these studies will examine 1) the efficacy of antiresorptive therapy in slowing the bone loss that occurs with decreased of mechanical loading, and 2) the role of the bone anabolic agent, PTH, in accelerating bone recovery and restoring bone strength. This research uses pharmacological agents that are already approved for clinical use; thus the findings from this research can be expected to see rapid implementation in bone loss situations occurring as a result of unloading, such as spinal cord injury and long-term immobilzation.

Task Progress & Bibliography Information FY2005 
Task Progress: We have initiated the immobilization phase of our new long-term studies, the toal duration of which will last 18 months from the start of each experiment. We have initiated new studies on a novel, structurally-based ultrasound procedure that significantly improves the prediction of mechanical properties by accounting for tissue anisotropy. In the first phase of this work, we used this novel, structurally-based ultrasound procedure to study bones from long-term immobilized animals. The second series of studies will examine bones from the current resorption suppression/remobilization + PTH experiments, as they become available.

Bibliography Type: Description: (Last Updated: 08/21/2020)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Li, C- Y C. Price; K. Delisser, P. Nasser, D. Laudier, M. O. Clement, K. J. Jepsen and M. B. Schaffler "Long-term disuse osteoporosis appears less sensitive to bisphosphonate treatment than other osteoporosis" N/A , Jan-2005
Articles in Peer-reviewed Journals Li, CY., C. Price, D. A. Laudier, R. J Majeska and M. B. Schaffler "Risedronate treatment only partially preserves cancellous bone mass and microarchitecture after long-term disuse" N/A , Jan-2006
Presentation Cardoso Landa, L; Seo, S; Jepsen, K J; Oddou, C; Meunier, A; Schaffler, M B "Ultrasonic characterization of anisotropic trabecular bone undergoing disuse osteoporosis with and without antiresorptive therapy" N/A

Feb-2005

Presentation Cardoso Landa, L; Seo, S; Jepsen, K J; Oddou, C; Meunier, A; Schaffler, M B. "Structurally-based ultrasonic approach of cancellous bone characterization" N/M

Feb-2005

Presentation Schaffler, M. B. "Bone Fragility" N/M

Dec-2004

Presentation Schaffler, M. B. "Bone Quality: What Is It and Can We Measure It?" N/M

May-2005

Presentation Schaffler, M. B. "Strength and Bone Quality" N/M

Apr-2005

Project Title:  BONE RECOVERY POTENTIAL AFTER BISPHOSPHONATE AND PTH TREATMENT OF DISUSE OSTEOPOROSIS Reduce
Fiscal Year: FY 2004 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2004  
End Date: 05/31/2008  
Task Last Updated: 04/03/2006 
Download report in PDF pdf
Principal Investigator/Affiliation:   Schaffler, Mitchell B. Ph.D. / Mount Sinai School of Medicine 
Address:  One Gustave L. Levy Place 
Box 1188 
New York , NY 10029-6500 
Email: Mitchell.Schaffler@mssm.edu 
Phone: 212-241-1625  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Mount Sinai School of Medicine 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. NCC 9-58-BL00406 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2003 Biomedical Research & Countermeasures 03-OBPR-04 
Grant/Contract No.: NCC 9-58-BL00406 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Osteo:Risk Of Early Onset Osteoporosis Due To Spaceflight (No longer used, July 2020)
Human Research Program Gaps: (1) B03:What pharmaceuticals against bone loss are best used and how? (merged into Osteo 7) (IRP Rev D)
Task Description: Bone loss in microgravity and the resulting bone fragility have been identified by NASA as key barriers to successful long-term space flight. Effective countermeasures must therefore prevent bone loss, but also to maintain the mechanical integrity of the tissue during prolonged space flight and allow rapid recovery of normal function. Disuse osteoporosis in humans and higher mammals results from elevated bone resorption. Thus, targeting osteoclasts with antiresorptive agents like bisphosphonate to prevent bone loss is a key strategy. While anti-resorptive drugs have been the cornerstones of osteoporosis therapy, anabolic agents, such as PTH, that stimulate bone formation represent an important new advance in the treatment of osteoporosis. We hypothesize that PTH may be especially valuable in reversing disuse if the deterioration of bone architecture can be slowed such that the anabolic agent has a better initial bone scaffold on which to work. The studies examine whether bone that remains after bisphosphonate-treatment during long-term immobilization can recover its architecture and mechanical function after restoration of mechanical usage (remobilization). We will then assess whether addition of anabolic PTH during immobilization will improve recovery of disuse bone. Recovery after long-term disuse with bisphosphonate treatment will be examined in an immobilization model. MicroCT imaging will be used to evaluate microstructure, biomechanical testing to assess function and histomorphometry to measure tissue physiological responses.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2004 
Task Progress: New project for FY2004; no progress report this period.

Bibliography Type: Description: (Last Updated: 08/21/2020)  Show Cumulative Bibliography Listing
 
 None in FY 2004