Severe Zinc Deficiency Impairs Accrual of Bone in Rapidly Growing Rats That Is Partially Corrected Following Short-term Zinc Repletion

Abstract

Zinc (Zn) deficiency impairs bone growth. However, the precise skeletal effects of varying levels of Zn deficiency and response to subsequent Zn repletion on the growing skeleton are incompletely understood. To address this gap in knowledge, we investigated the effects of dietary Zn ((severe deficiency (< 0.5 mg Zn/kg diet) and short-term Zn repletion (30 mg/kg diet), marginal deficiency (6 mg Zn/kg diet)) on bone mass, density, and cortical and cancellous bone microarchitecture in growing male Sprague Dawley rats. Marginal Zn intake for 42 days had no effect on bone mass or cortical and cancellous bone microarchitecture. Twenty-one days of severe Zn deficiency lowered serum osteocalcin and C terminal telopeptide of type I collagen (CTX-1), decreased tibial bone mineral content and density, and lowered cross-sectional volume, cortical volume, and cortical thickness in tibial diaphysis as compared to both Zn-adequate (30 mg/kg diet) and pair-fed controls. Severe Zn deficiency similarly lowered cancellous bone volume in proximal tibial metaphysis. Zn repletion (10 days) accelerated weight gain, indicative of catch-up growth, normalized CTX-1 and osteocalcin, but did not normalize bone mass (unadjusted and adjusted for body weight) or cortical and cancellous bone microarchitecture. In summary, severe but not marginal Zn deficiency in rapidly growing rats impaired acquisition of cortical and cancellous bone, resulting in abnormalities in bone microarchitecture. Zn repletion accelerated weight gain compared to Zn-adequate controls but absence of a compensatory increase in serum osteocalcin or bone mass suggests Zn repletion may be insufficient to fully counteract the detrimental effects of prior Zn deficiency on skeletal growth.

Keywords: Bone growth; Skeletal maturation; Zinc; Zinc deficiency; Zinc repletion.