Altered Trabecular Microarchitecture near the Glenohumeral Joint in a Rat Model of Neonatal Brachial Plexus Injury

McCORMICK, CAROLYN MARIE. Altered Trabecular Microarchitecture near the Glenohumeral Joint in a Rat Model of Neonatal Brachial Plexus Injury. (Under the direction of Jacqueline Cole and Katherine Saul). Neonatal brachial plexus injury (NBPI) occurs in nearly 1.5 of every 1000 infants during childbirth (Foad, Mehlman, & Ying, 2008), and 30-40% of these neonates sustain impaired function in the affected arm throughout their lifespan (Abzug, Kozin, & Zlotolow, 2015). Severity of upper limb paresis following NBPI may lead to reduced passive and active range of motion, including internal rotation contracture at the shoulder or flexion contracture at the elbow (Reading, Laor, Salisbury, Lippert, & Cornwall, 2012). Despite full neurologic recovery in 80-90% of affected children (Pearl, 2009), secondary glenohumeral deformities may still limit arm movement and hinder critical activities of daily living, such as eating and bathing. Abnormal development of muscle and bone at the shoulder is the most common reason for surgical intervention post-injury to improve functional outcomes (Abzug et al., 2015). However, very little is understood about parallel postnatal development of muscle and bone after peripheral nerve injury despite evidence that musculoskeletal deformities constrain movement, even after restored neurological function. Consequently, clinical management of secondary musculoskeletal deformity in the injured extremity has variable functional outcomes (Kozin, 2010). Regions in the glenohumeral joint experiencing abnormal growth and morphological deformities are comprised primarily of cancellous bone, which is integral to transfer of joint loading along the bone and is known to adapt to altered loads (Wolff, 1892/1986; Frost, 1994). This thesis examines underlying changes in cancellous bone in the glenohumeral joint using a rat model of NBPI. Sixteen Sprague-Dawley rat pups (Harlan Laboratories, Indianapolis, Indiana) received either neurectomy or sham surgery (n=8 each) five days postnatal in a prior study (Crouch et al., 2015). We assessed trabecular bone metrics, specifically bone mineral density (BMD), tissue mineral density (TMD), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness and separation (Tb.Th, and Tb.Sp) and their standard deviations (Tb.Th.SD, Tb.Sp.SD) using direct 3D methods (Bouxsein et al., 2010). Differences between neurectomy and sham groups were analyzed using two-tailed, unpaired t-tests. Differences between affected and contralateral limbs were analyzed using two-tailed, paired t-tests. Correlations between gross morphological bone measurements (humeral head superoinferior and anteroposterior translation and glenoid version and inclination) and trabecular bone metrics in the neurectomy scapulae and humeri were assessed using Pearson correlation tests. Changes in trabecular bone density and microarchitecture were similar in the humeral epiphysis and metaphysis. Trabecular TMD tended to be 4.5% lower in the neurectomy group than in the sham group (p=0.072 epiphysis, p=0.12 metaphysis). Trabecular thickness tended to be 12.5% lower in neurectomy relative to sham (p=0.076 epiphysis, p=0.057 metaphysis). BV/TV was not significantly different between groups (p=0.27 epiphysis, p=0.27 metaphysis), despite observing 14.4% reduction for neurectomy. Cancellous bone deterioration following neurectomy was also observed in the scapular glenoid. Relative to sham, the neurectomy group had significantly lower BV/TV (-18.6% in zone 2 in inferior glenoid underlying the fossa, p=0.0027) and Tb.N (-17.5 % in zone 3 in inferior glenoid near glenoid rim, p=0.011) and greater Tb.Sp (28.8% in zone 1 in subcoracoid region forming the superior glenoid, p=0.029 and 31.6% in zone 3, p=0.020). A trend for reduced BV/TV was observed in zone 3 (-4.95%) in neurectomy relative to sham (p=0.062). This thesis demonstrated that NBPI affects trabecular microarchitecture in addition to overall bone morphology. Our findings align with other reports of compromised trabecular bone following NBPI (Kim, Galatz, Das, Patel, & Thomopoulos, 2010). Further investigation is needed to understand whether NBPI causes overall weaker bone strength in the shoulder. A more in-depth understanding about postnatal glenohumeral development may inform therapies and treatments that maximize shoulder movement and minimize bone damage.