Lead induced differences in bone properties in osteocalcin +/+ and -/- female mice

G Yildirim; W C Budell; O Berezovska; S Yagerman; S S Maliath; P Mastrokostas; S Tommasini; T L Dowd

doi:10.1016/j.bonr.2023.101672

Lead induced differences in bone properties in osteocalcin +/+ and -/- female mice

Bone Rep. 2023 Mar 17:18:101672. doi: 10.1016/j.bonr.2023.101672. eCollection 2023 Jun.

Authors

G Yildirim¹, W C Budell¹, O Berezovska¹, S Yagerman², S S Maliath¹, P Mastrokostas¹, S Tommasini³, T L Dowd^{1

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Affiliations

¹ Department of Chemistry, Brooklyn College of the City University of New York, Brooklyn, NY, USA.
² Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
³ Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
⁴ Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.
⁵ Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.

Abstract

Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodeling and is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC-/- mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly increased turnover in OC+/+ and in OC-/- bones producing increased total volume, area and marrow area/total area with decreased BV/TV compared to controls. The increased turnover decreased mineral/matrix vs. Oc+/+ and increased mineral/matrix and crystallinity vs. OC-/-. PbOC-/- had increased bone formation, cross-sectional area (Imin) and decreased collagen maturity compared OC-/- and PbOC+/+. Imbalanced turnover in PbOC-/- confirmed the role of osteocalcin as a coupler of formation and resorption. Bone strength and stiffness were reduced in OC-/- and PbOC-/- due to reduced material properties vs. OC+/+ and PbOC+/+ respectively. The PbOC-/- bones had increased area to compensate for weaker material properties but were not proportionally stronger for increased size. However, at low lead levels osteocalcin plays the major role in bone strength suggesting increased fracture risk in low Pb²⁺ exposed elderly could be due to reduced osteocalcin as well. Years of low lead exposure or higher blood lead levels may have an additional effect on bone strength.

Keywords: Biomechanics; FTIRI; Mice; MicroCT; Osteocalcin knock-out mouse; Pb2+ toxicity.