Altered Trabecular Microarchitecture Near the Glenohumeral Joint of a Rat Model With Neonatal Brachial Plexus Injury

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URL: http://www.lib.ncsu.edu/resolver/1840.20/34651

Abstract

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

Cited Works (18)

Year	Entry
2007	Delp SL, Anderson FC, Arnold AS, Loan P, Habib A, John CT, Guendelman E, Thelen DG. OpenSim: open-source software to create and analyze dynamic simulations of movement. IEEE Trans Biomed Eng. November 2007;54(11):1940-1950.
1983	Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis: implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. October 1983;72(4):1396-1409.
2010	Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. July 2010;25(7):1468-1486.
2000	Vico L, Collet P, Guignandon A, Lafage-Proust M-H, Thomas T, Rehailia M, Alexandre C. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet. May 6, 2000;355(9215):1607-1611.
2014	Zhou BO, Yue R, Murphy MM, Peyer JG, Morrison SJ. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell. August 7, 2014;15(2):154-168.
1986	Wolff J. The Law of Bone Remodelling. Maquet P, Furlong R, trans. New York, NY: Springer; 1986.
1997	Prendergast PJ, Huiskes R, Søballe K. Biophysical stimuli on cells during tissue differentiation at implant interfaces. J Biomech. June 1997;30(6):539-548.
2011	Cole JH, van der Meulen MCH. Whole bone mechanics and bone quality. Clin Orthop Relat Res. August 2011;469(8):2139-2149.
1998	Carter DR, Beaupré GS, Giori NJ, Helms JA. Mechanobiology of skeletal regeneration. Clin Orthop Relat Res. October 1998;355(suppl):S41-S55.
1977	Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59A(7):954-962.
1998	Turner CH. Three rules for bone adaptation to mechanical stimuli. Bone. November 1998;23(5):399-407.
2004	Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long‐duration spaceflight. J Bone Miner Res. June 2004;19(6):1006-1012.
2001	van der Meulen MCH, Jepsen KJ, Mikić B. Understanding bone strength: size isn’t everything. Bone. July 2001;29(1):101-104.
2000	Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD. Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature. June 8, 2000;405(6787):704-706.
2000	Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, Basle M, Audran M. Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res. January 2000;15(1):13-19.
1994	Mullender MG, Huiskes R, Weinans H. A physiological approach to the simulation of bone remodeling as a self-organizational control process. J Biomech. November 1994;27(11):1389-1394.
2001	Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecular bone. Annu Rev Biomed Eng. 2001;3:307-333.
1994	Frost HM. Wolff's law and bone's structural adaptations to mechanical usage: an overview for clinicians. Angle Orthod. June 1994;64(3):175-188.