Severe injury-induced osteoporosis and skeletal muscle mineralization: Are these related complications?
Stephanie N. Moore-Lotridge,
Rivka Ihejirika,
Breanne H.Y. Gibson,
Samuel L. Posey,
Nicholas A. Mignemi,
Heather A. Cole,
Gregory D. Hawley,
Sasidhar Uppuganti,
Jeffry S. Nyman,
Jonathan G. Schoenecker
Affiliations
Stephanie N. Moore-Lotridge
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center of Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Rivka Ihejirika
Vanderbilt University Medical School, Vanderbilt University, Nashville, TN 37232, USA
Breanne H.Y. Gibson
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
Samuel L. Posey
Vanderbilt University Medical School, Vanderbilt University, Nashville, TN 37232, USA
Nicholas A. Mignemi
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Heather A. Cole
Department of Nuclear Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Gregory D. Hawley
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Sasidhar Uppuganti
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center of Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Tennessee Valley Healthcare System, Vanderbilt University, Nashville, TN 37232, USA
Jeffry S. Nyman
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center of Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Tennessee Valley Healthcare System, Vanderbilt University, Nashville, TN 37232, USA
Jonathan G. Schoenecker
Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center of Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Corresponding author at: 2200 Children's Way, Nashville, TN 37232-9565, USA.
Severely injured patients are beleaguered by complications during convalescence, such as dysregulated biomineralization. Paradoxically, severely injured patients experience the loss of bone (osteoporosis), resulting in diminished skeletal integrity and increased risk of fragility fractures; yet they also accrue mineralization in soft tissues, resulting in complications such as heterotopic ossification (HO). The pathophysiology leading to dysregulated biomineralization in severely injured patients is not well defined. It has been postulated that these pathologies are linked, such that mineralization is “transferred” from the bone to soft tissue compartments. The goal of this study was to determine if severe injury-induced osteoporosis and soft tissue calcification are temporally coincident following injury. Using a murine model of combined burn and skeletal muscle injury to model severe injury, it was determined that mice developed significant progressive bone loss, detectable as early as 3 days post injury, and marked soft tissue mineralization by 7 days after injury. The observed temporal concordance between the development of severe injury-induced osteoporosis and soft tissue mineralization indicates the plausibility that these complications share a common pathophysiology, though further experiments are required.
