Joshua Yarrow MS, PhD, FACSM

Research Interest

My research spans the preclinical-translational-clinical spectrum and focuses broadly on determining how the endocrine and nervous systems regulate bone and muscle integrity, along with cardiometabolic and prostate health in adulthood, with two primary themes:

1. determining the sex-steroid hormone-mediated mechanisms that underlie maintenance of bone, muscle, and adiposity, and that influence cardiovascular and prostate health in adults and
2. evaluating pharmacologic and activity-based physical therapy interventions to enhance musculoskeletal integrity and promote use-dependent neuromuscular plasticity after spinal cord injury (SCI) and in the aging population.

My preclinical research program is funded to evaluate the individual and combined effects of physical rehabilitation and anabolic adjuvants on muscle, bone, and locomotor recovery after SCI. I am also the Principal Investigator of a Phase II randomized clinical trial that is evaluating the effects of testosterone plus finasteride (a type II 5α-reductase inhibitor) on musculoskeletal recovery, body composition, and metabolic and prostate health in hypogonadal men with ambulatory dysfunction resulting from incomplete SCI and on small Phase II feasibility trial that is evaluating testosterone plus locomotor training on recovery of musculoskeletal integrity and walking function after SCI.

In addition, I served as Founding Director of the Preclinical Musculoskeletal Imaging Core Lab at North Florida/South Georgia Veterans Health System, which is a national resource for imaging of bone, vascular, and soft-tissue morphology in rodents and other small lab animals using microcomputed tomography (microCT) and dual-energy x-ray absorptiometry (DEXA).

Grants & Funding

Influence of NOX4 inhibition on muscle fibrosis after spinal cord injury

Role: Co-PI
The study will
1) determine the ability of NOX4 inhibition to prevent and/or reverse muscle fibrosis and promote muscle recovery in a rat severe SCI model and 
2) assess the magnitude to which NOX4 inhibition alters downstream cellular and molecular changes associated with fibrotic infiltration of muscle after SCI. 
Funder: VA RRD SPiRE

Reliability and Validity of Preclinical DEXA Imaging

Role: PI
This study will assess the reliability, validity, and sensitivity / accuracy of a new commercially available rodent in vivo dual-energy x-ray absorptiometry (DEXA) system.
Funder: MicroPhotonics, Inc.

Development and Validation of a Rodent FES Bicycle System

Role: PI
More than 42,000 individuals with spinal cord injury (SCI) are eligible for treatment in the VA Healthcare System, with direct healthcare expenditures exceeding $716 million/year. Bone loss is a hallmark of severe SCI, producing 20- to 100-fold higher fracture risk, with extended post-fracture hospitalization. Moreover, the risk for respiratory illness, venous thromboembolic events, pressure ulcers, urinary tract infections, and other medical comorbidities more than doubles in persons with SCI within 1-month of fracture, which contributes to the 30% higher 5-yr mortality risk that exists for those with versus without fracture after SCI. 
Despite these consequences, no physical rehabilitation regimen or pharmacologic therapy has been shown to consistently improve BMD recovery after SCI or completely prevent bone loss at this population's most fracture-prone sites. These findings provide strong justification for studies that focus on identifying and optimizing strategies to improve skeletal integrity and reduce fracture incidence in Veterans with SCI.
Funder: VA RRD SPiRE
NIH website

Locomotor Training with Anabolic Adjuvants for Musculoskeletal Recovery After SCI

Role: PI
More than 42,000 individuals with spinal cord injury (SCI) are eligible for treatment in the VA Healthcare System, with direct healthcare expenditures exceeding $716 million/year. Severe muscle and bone deficits are hallmark consequences of functionally complete SCI that worsen metabolic co-morbidities, increase bone fracture risk, and impede successful physical rehabilitation. 
No stand-alone pharmacologic or mechanical reloading strategy simultaneously regenerates muscle and bone after SCI. A significant need exists to identify novel therapeutic approaches that can be used with physical rehabilitation to promote musculoskeletal recovery after SCI.
Funder: VA RRD SPiRE
NIH website
Publications of note:
— Passive Cycle Training Promotes Bone Recovery after Spinal Cord Injury without Altering Resting-State Bone Perfusion
— Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury
— Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury

ShEEP Request for High Resolution Desktop MicroCT System

Role: PI
Many scientists at our VA station are evaluating bone, vascular, and soft tissue responses to neurotrauma, obesity, osteoporosis, cancer, and other prevalent chronic health conditions in Veterans. Much of this work requires high-resolution 3D imaging of the microstructure of excised bone and vasculature, which has been facilitated for > 10 years by a desktop microCT system in our centralized preclinical imaging core facility. 
This grant seeks to acquire a Bruker Skyscan 1272 (new model) high-resolution microCT system to replace our current desktop microCT system, which has reached its expected end-of-life, along with accessories that will improve our imaging capabilities, increase device availability, and reduce long-term operational costs. 
Access to this device will ensure continuity in high-resolution 3D imaging services available at our facility, which is needed for ongoing and future studies focused on improving Veterans’ health.
Funder: VA RRD SPiRE
NIH website

Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI

Role: PI
More than 42,000 individuals with spinal cord injury (SCI) are eligible for treatment in the VA Healthcare System (i.e., 16% of the entire SCI population), resulting in direct healthcare expenditures exceeding $716 million annually. The average direct and indirect per-patient costs associated with the first-year medical treatment of motor incomplete SCIs is $218,000 within the VA, with subsequent yearly expenditures averaging $21,450. 
These costs are exacerbated by the myriad of functional and physiologic deficits following SCI, of which reduced lower extremity musculoskeletal integrity, impaired neuromuscular force production, and elevated visceral adiposity are hallmark characteristics. These maladaptive changes represent fundamental impediments to rehabilitation strategies intended to maximize physical function and restore health after SCI. 
Identifying novel strategies that safely enhance musculoskeletal integrity/function and improve body composition may improve health and reduce disability within this population.
Funder: Veterans Affairs
NIH website

Role Of Bone Blood Flow In Bone Loss Following SCI

Role: PI
Bone loss following spinal cord injury (SCI) is an essential problem for Veterans. Among those with functionally complete SCI, there is a 100-fold increase in fracture risk. Although bisphosphonates are currently used to protect bone in SCI patients, recent studies show these drugs are ineffective in the SCI population. Thus, new strategies for protecting bone mass after SCI are urgently needed. 
Our study will test, in a rat model, 1) whether loss of blood supply to the bone is a cause of bone loss following SCI and 2) whether multi-modal therapy (administration of the vascular protective agent tetramethylpyrazine (TMP) and/or passive motorized bicycle training) can prevent loss of blood flow and loss of bone mineral after SCI. This preclinical study has translational value because it will test a strategy that can be later applied in a clinical trial to prevent bone loss in Veterans with SCI.
Funder: Veterans Affairs
NIH website
Publications of note:
— Passive Cycle Training Promotes Bone Recovery after Spinal Cord Injury without Altering Resting-State Bone Perfusion
— Bone loss after severe spinal cord injury coincides with reduced bone formation and precedes bone blood flow deficits

Locomotor Training with Testosterone to Promote Bone and Muscle Health after SCI

Role: PI
The goal of this study is to determine the feasibility of implementing locomotor training plus testosterone replacement therapy in men with low testosterone and ambulatory dysfunction after chronic incomplete SCI and to collect pilot data on musculoskeletal and walking recovery.
Funder: Craig H. Neilsen Foundation, Spinal Cord Injury Research on the Translational Spectrum (SCIRTS)

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Recent Publications

2024

Kura JR, Cheung B, Conover CF, Wnek RD, Reynolds MC, Buckley KH, Soto BM, Otzel DM, Aguirre JI, Yarrow JF. PASSIVE BICYCLE TRAINING STIMULATES EPIPHYSEAL BONE FORMATION AND RESTORES BONE INTEGRITY INDEPENDENT OF LOCOMOTOR RECOVERY IN A RAT SPINAL CORD INJURY MODEL. J Appl Physiol (1985). 2024 Aug 1. doi: 10.1152/japplphysiol.00299.2024. Epub ahead of print. PMID: 39088645.

Kok HJ, Fletcher DB, Oster JC, Conover CF, Barton ER, Yarrow JF. Transcriptomics reveals transient and dynamic muscle fibrosis and atrophy differences following spinal cord injury in rats. J Cachexia Sarcopenia Muscle. 2024 May 19. doi: 10.1002/jcsm.13476. Epub ahead of print. PMID: 38764311.

2023

Castillo EJ, Jiron JM, Croft CS, Freehill DG, Castillo CM, Kura J, Yarrow JF, Bhattacharyya I, Kimmel DB, Aguirre JI. Intermittent parathyroid hormone enhances the healing of medication-related osteonecrosis of the jaw lesions in rice rats. Front Med (Lausanne). 2023 Jun 19;10:1179350. doi: 10.3389/fmed.2023.1179350. PMCID: PMC10315582.

Yarrow JF, Wnek RD, Conover CF, Reynolds MC, Buckley KH, Kura JR, Sutor TW, Otzel DM, Mattingly AJ, Borst SE, Croft SM, Aguirre JI, Beck DT, McCullough DJ. Passive Cycle Training Promotes Bone Recovery after Spinal Cord Injury without Altering Resting-State Bone Perfusion. Med Sci Sports Exerc. 2023 May 1;55(5):813-823. doi: 10.1249/MSS.0000000000003101. Epub 2022 Dec 13. PMCID: PMC10090357.

2022

Sutor TW, Kura J, Mattingly AJ, Otzel DM, Yarrow JF. The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury. Int J Mol Sci. 2022 Jan 6;23(2):608. doi: 10.3390/ijms23020608. PMCID: PMC8775843.

2021

Cameron ME, Underwood PW, Williams IE, George TJ, Judge SM, Yarrow JF, Trevino JG, Judge AR. Osteopenia is associated with wasting in pancreatic adenocarcinoma and predicts survival after surgery. Cancer Med. 2022 Jan;11(1):50-60. doi: 10.1002/cam4.4416. Epub 2021 Nov 17. PMCID: PMC8704155.

Yarrow JF, Wnek RD, Conover CF, Reynolds MC, Buckley KH, Kura JR, Sutor TW, Otzel DM, Mattingly AJ, Croft S, Aguirre JI, Borst SE, Beck DT, McCullough DJ. Bone loss after severe spinal cord injury coincides with reduced bone formation and precedes bone blood flow deficits. J Appl Physiol (1985). 2021 Oct 1;131(4):1288-1299. doi: 10.1152/japplphysiol.00444.2021. Epub 2021 Sep 2. PMCID: PMC8560388.

Snyder AR, Greif SM, Clugston JR, FitzGerald DB, Yarrow JF, Babikian T, Giza CC, Thompson FJ, Bauer RM. The Effect of Aerobic Exercise on Concussion Recovery: A Pilot Clinical Trial. J Int Neuropsychol Soc. 2021 Sep;27(8):790-804. doi: 10.1017/S1355617721000886. PMCID: PMC8601125. PMID: 34548116

Otzel DM, Kok HJ, Graham ZA, Barton ER, Yarrow JF. Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury. Curr Opin Pharmacol. 2021 Oct;60:193-199. doi: 10.1016/j.coph.2021.07.023. Epub 2021 Aug 28. PMCID: PMC9190029. PMID: 34461564

Media

Manipulating Androgen Metabolism: Preclinical & Clinical Endeavors to Improve Testosterone Efficacy & Limit Side Effects

by Josh Yarrow
15 February 2024

Watch: Manipulating Androgen Metabolism: Preclinical & Clinical Endeavors to Improve Testosterone Efficacy & Limit Side Effects