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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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Moore-Lotridge has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Dr. Ihejirka has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Ms. Gibson has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Dr. Posey is a member of the U.S. Air Force. The views expressed in this article are those of the author and do not reflect the official policy or position of the United States Air Force, Department of Defense, or the U.S. Government.Dr. Mignemi has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Dr. Cole has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Mr. Hawley has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Mr. Uppuganti has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Dr. Nyman has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Dr. Schoeencker is a member of the education advisory board at OrthoPediatrics, receives research funding from OrthoPediatrics, and research support from IONIS Pharmaceuticals, PXE International, the United States Department of Defense, and the National Institutes of Health., (© 2020 The Authors.)