Dixit, N. N. | bioRxiv Science

bioRxiv2025

Brachial Plexus Birth Injury Causes Location-Dependent Detriments in Glenohumeral Trabecular Bone Microstructure

Brachial plexus birth injury (BPBI) is caused during a difficult childbirth when the head and neck are excessively stretched, and the brachial plexus nerve bundle is damaged. Injury causes lifelong arm impairment in 30-40% of those affected, but the extent to which bone microstructure is affected and how that relates to bone morphology alterations is unclear. Additionally, how injury location impacts trabecular bone, and the role limb disuse plays in these differential effects are unknown. Using two rat models of BPBI (postganglionic and preganglionic) and a disuse model (disarticulation), trabecular bone microstructure and glenohumeral morphology were characterized in the proximal humerus and distal scapula. For bone microstructure, the regions closest to the joint articulating surface incurred the greatest detriments with the least robust trabecular bone. These trabecular bone deficits in the humeral epiphysis and scapular neck were greater following preganglionic injury than postganglionic injury. The effects in the disarticulation group tended to align more with those in the postganglionic group, and greater detriments were observed in the scapula than in the humerus. Bone morphology metrics were explained mainly by quantity and architecture of trabecular bone but were not explained by the same metrics across all groups. Combining results with changes in bone morphology, data suggest differential effects with injury location and the effects of limb disuse to be most prominent in the postganglionic injury group and the distal scapula. In addition, the differences in results between postganglionic and preganglionic and macrostructural and microstructural deformity, suggest different drivers for postganglionic and preganglionic injuries and different factors causing macrostructural and microstructural alterations.

bioengineering↗

bioRxiv2025

Bone Mineralization and Metabolism are Altered in a Rat Model of Brachial Plexus Birth Injury

Brachial plexus birth injury (BPBI) is a common nerve injury incurred during a difficult childbirth when the brachial plexus nerve bundle is excessively stretched, resulting in functional arm impairment in 30-40% of those affected. Injury can present in two different locations, modeled in rats as postganglionic and preganglionic neurectomies. Osseous deformities are present following both injury types. However, the underlying factors behind these deformities are not fully understood. While past studies have explored muscle structure and altered mechanical joint loading as factors, bone metabolism, muscle composition, and muscle-bone crosstalk have not been fully explored. Using postganglionic and preganglionic BPBI rat models and a disuse model, bone metabolism, muscle composition, and muscle-bone crosstalk were explored. Dynamic histomorphometry and similar methods were used to characterize humeral growth and humeral growth plate activity to understand bone metabolism, muscle fibrosis was analyzed to assess muscle composition, and FGF-2 quantification was performed to assess muscle-bone crosstalk. Postganglionic injury portrayed more changes in the humeral diaphyseal region than preganglionic and displayed reduced bone metabolism on the endosteal surface while preganglionic displayed reduced bone metabolism on the periosteal surface. However, only preganglionic showed significantly lower growth plate activity. In regards to fibrosis, both injury types showed fibrosis in the biceps but only preganglionic showed fibrosis in the subscapularis. The limb disuse model did not show fibrosis. Additionally, preganglionic had an increased production of FGF-2 signaling more so in the subscapularis. Overall, deformities from postganglionic injury may be from bone formation and bone resorption while deformities from preganglionic injury are likely from an overall reduction in bone growth that is not solely from limb disuse. The fibrosis and FGF-2 signaling alterations seen are not likely to be the direct cause of osseous deformity and the drivers behind the alterations are likely different between postganglionic and preganglionic injuries.

bioengineering↗