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Effect of Osseointegrated Prostheses on the Pathogenesis of Hip Osteoarthritis in Patients with Lower Limb Loss

Award Number: K01AR080776
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/03/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Effect of Osseointegrated Prostheses on the Pathogenesis of Hip Osteoarthritis in Patients with Lower Limb Loss - PROJECT SUMMARY The overarching objective of this proposal is to determine if transfemoral osseointegrated prostheses have a positive influence on the etiology of hip osteoarthritis (OA). The two leading causes of disability following transfemoral amputation are chronic skin pathologies due to poor socket fit (e.g., ulceration) and OA due to habitually altered joint loading. Osseointegrated prostheses are a recent clinical intervention to treat socket related pathologies by directly mounting the prosthesis to the residual limb through a bone anchored implant, providing a more normative load transmission from the ground to residual limb. This proposal will determine if this improved load transmission has positive role on the pathogenesis of hip OA differently than socket prostheses. This will be accomplished through a longitudinal study design that will compare the most common biomechanical etiological factors to OA progression at two timepoints (baseline and 12-months) between two groups (patients with osseointegrated prostheses and patients who successfully use a traditional socket prosthesis). In Aim 1, we will quantify bilateral hip muscle quality using fat fraction quantitative magnetic resonance imaging (MRI). Using these images, we will quantify 3D muscle volume and levels of fatty infiltration on the bilateral hip musculature. This will elucidate if the known atrophy and poor composition due to disuse in a socket prosthesis, both of which are known to progress OA, can be reversed following prosthesis osseointegration. In Aim 2, we will quantify dynamic cartilage loading mechanics using motion capture and a subject-specific musculoskeletal contact model. Because altered cartilage loading is a primary instigator and factor in OA onset and progression, these results will determine if cartilage mechanics are normalized during activities of daily living following osseointegration. Although muscle composition and cartilage mechanics are etiological factors to OA development, we seek to assess the role of osseointegration on the clinical progression of OA. Thus, in Aim 3, we will quantify cartilage health using T2 quantitative MRI, which is currently the most sensitive methodology to assess early osteoarthritic changes in-vivo. Ultimately, we seek to use our multi-domain approach to better inform targeted interventions aimed at improving outcomes following osseointegration. The candidate’s overarching career goal is to utilize engineering-based tools to better elucidate the mechanisms to secondary pain conditions that can be used to improve targeted interventions. This proposal builds on the candidate’s current expertise by providing new training in quantitative MRI, advanced imaging post- processing tools, longitudinal research design and implementation, and links between biomechanics and clinical factors of joint disease. The mentoring team consists of physical therapists, radiologists, bioengineers, and orthopaedic surgeons who are experts in imaging, clinical interventions, and OA. This proposal will provide preliminary data for an R01 focused on key factors that affect long-term outcomes with varying prosthesis types.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $127,378 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	1/27/2026	NON-COMPETING CONTINUATION	$127,378
														Subtotal = $127,378

Issue Date FY: 2025 ( Subtotal = $131,625 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	12/6/2024	NON-COMPETING CONTINUATION	$131,625
														Subtotal = $131,625

Issue Date FY: 2024 ( Subtotal = $131,625 )
2024	2024	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/13/2023	NON-COMPETING CONTINUATION	$131,625
														Subtotal = $131,625

Issue Date FY: 2023 ( Subtotal = $131,625 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/3/2023	NEW	$131,625
														Subtotal = $131,625

Grand Total All Awards = $522,253

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Effect of Osseointegrated Prostheses on the Pathogenesis of Hip Osteoarthritis in Patients with Lower Limb Loss

Award Number: K01AR080776

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/03/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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