Image-based radiodensity profilometry measures early remodeling at the bone-callus interface in sheep

Abstract

Bone healing has been traditionally described as a four-phase process: inflammatory response, soft callus formation, hard callus development, and remodeling. The remodeling phase has been largely neglected in most numerical mechanoregulation models of fracture repair in favor of capturing early healing using a pre-defined callus domain. However, in vivo evidence suggests that remodeling occurs concurrently with repair and causes changes in cortical bone adjacent to callus that are typically neglected in numerical models of bone healing. The objective of this study was to use image processing techniques to quantify this early-stage remodeling in ovine osteotomies. To accomplish this, we developed a numerical method for radiodensity profilometry with optimization-based curve fitting to mathematically model the bone density gradients in the radial direction across the cortical wall and callus. After assessing data from 26 sheep, we defined a dimensionless density fitting function that revealed significant remodeling occurring in the cortical wall adjacent to callus during early healing, a 23% average reduction in density compared to intact. This fitting function is robust for modeling radial density gradients in both intact bone and fracture repair scenarios and can capture a wide variety of the healing responses.The fitting function can also be scaled easily for comparison to numerical model predictions and may be useful for validating future mechanoregulatory models of coupled fracture repair and remodeling.

Embracing ethical research: Implementing the 3R principles into fracture healing research for sustainable scientific progress

“…4,5 Although it is commonly noted that remodeling is the final stage of bone healing, it has been shown that remodeling occurs in tandem with callus formation in the earliest stages of fracture repair. 10,11 To study this complex process, researchers choose model systems and experimental methods based on the desired mechanistic or outcome-oriented insights needed to test their hypotheses. Some experiments seek to mimic as many aspects of human fractures as possible, while others use highly standardized surgeries and genetically inbred animal models.…”

“…Finally, bone remodeling commences, which consists of an intricate balance between resorption of the cartilage callus and primary bone in coupled remodeling 4,5 . Although it is commonly noted that remodeling is the final stage of bone healing, it has been shown that remodeling occurs in tandem with callus formation in the earliest stages of fracture repair 10,11 …”