Effects of reproduction and lactation on the functional spinal unit post menopause

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Project Summary/Abstract Lactation and menopause are physiological events where substantial changes in mineral and skeletal metabolism are triggered by a shared endocrine signal of rapid estrogen decline, resulting in bone loss. Consequently, low back pain, particularly during childbearing and post menopause is commonly associated with intervertebral disc degeneration (IVDD) and osteoporosis of vertebral bone. Clinical investigations suggested that no or negative effect of parity on self-reported LBP while a recent case-control study reported breastfeeding as a protective factor for clinically diagnosed IVDD in elderly women. As a result, there exists a critical knowledge gap regarding the effects of reproduction and lactation on the FSU that are independent of non-biological effects of parenthood. As the functional spinal unit (FSU) consists of vertebral bone (VB), cartilage end plate (CEP), and intervertebral disc (IVD), understanding the interactive effects of reproduction and menopause on CEP and IVD homeostasis is essential to uncover possible mechanisms of how the FSU changes to accommodate demanding metabolic conditions. Our research group has previously reported significant vertebral bone loss during pregnancy and lactation followed by a rapid recovery post-weaning. Moreover, a history of lactation exerts a protective effect on VB against post-menopausal osteoporosis. In particular, perilacunar-canalicular (PLC) remodeling activities are significantly increased in rats with reproductive history post-OVX, which would likely lead to increased solute transport within the lacunar-canalicular system, and the subsequent altered nutrition delivery and transport between VB and CEP may impact IVD health. Therefore, we hypothesize that a similar innate compensatory mechanism from reproduction may protect against post-menopausal IVDD by enhancing the local nutrient delivery and transport within the FSU resulting from increased PLC remodeling. The objective of this proposal is to establish and monitor changes of intervertebral disc degeneration in the FSU in response to estrogen deficiency and identify possible mechanisms that may differentiate responses in rats with and without a reproduction history. We will (1) establish an animal model to determine the biological effect of reproduction and lactation on IVD tissue and establish a direct connection between reproduction and menopause by investigating their interactive effects on IVD health; (2) Focus on local solute transport at the bone and CEP interface; (3) Reveal novel functions of the osteocyte PLC remodeling in modulating nutrient transport across IVD-CEP-VB functional unit; (4) Develop and utilize imaging modalities (in vivo µCT and quantitative MRI T1 and T2 mapping) to track the structural changes of IVD-CEP-VB functional unit and examine solute diffusivity of the IVD. Elucidating the biological effects of reproduction and lactation on the FSU will provide clinical insight on whether preventative measures need to be taken for postmenopausal women by considering their status and history of reproduction and lactation.