Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation
Purpose of review
This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an effort to elucidate how the balance between the structural and metabolic functions of the skeleton is achieved during these physiological processes.
While pregnancy and lactation induce significant changes in bone density and structure to provide calcium for fetal/infant growth, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity. Both clinical and animal studies suggest that pregnancy and lactation lead to adaptations in cortical bone structure to allow for rapid calcium release from the trabecular compartment while maintaining whole bone stiffness and strength. Moreover, extents of lactation-induced bone loss and weaning-induced recovery are highly dependent on a given bone’s load-bearing function, resulting in better protection of the mechanical integrity at critical load-bearing sites. The recent discovery of lactation-induced osteocytic perilacunar/canalicular remodeling (PLR) indicates a new means for osteocytes to modulate mineral homeostasis and tissue-level mechanical properties of the maternal skeleton. Furthermore, lactation-induced PLR may also play an important role in maintaining the maternal skeleton’s load-bearing capacity by altering osteocyte’s microenvironment and modulating the transmission of anabolic mechanical signals to osteocytes.
Both clinical and animal studies show that parity and lactation have no adverse, or a positive effect on bone strength later in life. The skeletal effects during pregnancy and lactation reflect an optimized balance between the mechanical and metabolic functions of the skeleton.
KeywordsBone structure Bone mechanics Pregnancy Lactation Bone adaptation Perilacunar/canalicular remodeling (PLR) Bone fluid flow Osteocyte
This work was supported by NIH K01-AR066743 (to XSL), NIH R01-AR071718 (to XSL), NIH R01-AR054385 (to LW), and NSF #1653216 (to XSL).
Compliance with Ethical Standards
Conflict of Interest
X. Sherry Liu, Liyun Wang, Chantal M. J. de Bakker, and Xiaohan Lai declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.2017 Global health observatory data. World Health Organization.Google Scholar
- 2.Horta BL, Victora CG. Long-term effects of breastfeeding. World Health Organization; 2013.Google Scholar
- 3.Global Nutrition Targets 2025: Breastfeeding policy brief. World Health Organization, UNICEF; 2014.Google Scholar
- 4.• Kovacs CS. Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev. 2016;96(2):449–547 This paper provided a comprehensive review on skeletal and mineral physiology of the maternal skeleton and disorders of bone and mineral metabolism during pregnancy, lactation, and post-weaning recovery. CrossRefGoogle Scholar
- 15.Collins JN, Kirby BJ, Woodrow JP, Gagel RF, Rosen CJ, Sims NA, et al. Lactating Ctcgrp nulls lose twice the normal bone mineral content due to fewer osteoblasts and more osteoclasts, whereas bone mass is fully restored after weaning in association with up-regulation of Wnt signaling and other novel genes. Endocrinology. 2013;154(4):1400–13.PubMedPubMedCentralCrossRefGoogle Scholar
- 18.• de Bakker CMJ, Tseng WJ, Li Y, Zhao H, Altman-Singles AR, Jeong Y, et al. Reproduction differentially affects trabecular bone depending on its mechanical versus metabolic role. J Biomech Eng. 2017;139(11) This study quantified the proportion of the load carried by the trabeculae, as well as the extent of reproductive loss and recovery in bone volume, structure, cellular activities, and mechanical properties, at two distinct skeletal sites: the tibia and lumbar vertebra. The differential trabecular response indicate differences in the extent of the trabecular bone’s structural vs. metabolic functions at these two locations. Google Scholar
- 21.• Kaya S, Basta-Pljakic J, Seref-Ferlengez Z, Majeska RJ, Cardoso L, Bromage TG, et al. Lactation-induced changes in the volume of osteocyte lacunar-canalicular space alter mechanical properties in cortical bone tissue. J Bone Miner Res. 2017;32(4):688–97 This study demonstrates that tissue-level cortical bone mechanical properties are rapidly and reversibly modulated by osteocytes in response to lactation and weaning. PubMedCrossRefGoogle Scholar
- 26.Seriwatanachai D, Thongchote K, Charoenphandhu N, Pandaranandaka J, Tudpor K, Teerapornpuntakit J, et al. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio. Bone. 2008;42(3):535–46.PubMedCrossRefGoogle Scholar
- 29.Ardeshirpour L, Dann P, Adams DJ, Nelson T, VanHouten J, Horowitz MC, et al. Weaning triggers a decrease in receptor activator of nuclear factor-kappaB ligand expression, widespread osteoclast apoptosis, and rapid recovery of bone mass after lactation in mice. Endocrinology. 2007;148(8):3875–86.PubMedCrossRefGoogle Scholar
- 44.• de Bakker CM, Altman-Singles AR, Li Y, Tseng WJ, Li C, Liu XS. Adaptations in the Microarchitecture and load distribution of maternal cortical and trabecular bone in response to multiple reproductive cycles in rats. J Bone Miner Res. 2017;32(5):1014–26 This study longitudinally tracked the bone structural changes in rat proximal tibia in response to 3 reproductive cycles and demonstrated that pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure, improvement in the robustness of cortical bone, and increased proportion of the total load carried by the cortical bone, allowing the overall mechanical function of the tibia to be maintained. PubMedPubMedCentralCrossRefGoogle Scholar
- 51.Brembeck P, Winkvist A, Ohlsson C, Lorentzon M, Augustin H. Determinants of microstructural, dimensional and bone mineral changes postpartum in Swedish women. Br J Nutr. 2016:1–9.Google Scholar
- 52.Kokolus S, Vrabel MB, Liu XS, Boutroy S, Rogers H, McMahon D, et al. High resolution peripheral quantitative CT (HRpQCT) reveals preferential inner trabecular bone loss in lactating women. American Society for Bone and Mineral Research Annual Meeting; 2010; Toronto. Canada. .Google Scholar
- 53.Kepley A, Boutroy S, Zhang C, Bucovsky M, Vrabel MB, Kokolus S, et al. In breastfeeding women, trabecular bone loss at the radius, seen by high resolution peripheral quantitative CT (HRpQCT), persists at 18 months postpartum. American Society of Bone and Mineral Research Annual Meeting; 2012; Minneapolis, MN.Google Scholar
- 59.de Bakker CMJ, Zhao H, Tseng WJ, Li Y, Altman-Singles AR, Liu Y, et al. Effects of reproduction on sexual dimorphisms in rat bone mechanics. J Biomech. 2018.Google Scholar
- 62.ACOG Committee Opinion No. 650: Physical activity and exercise during pregnancy and the postpartum period. Obstet Gynecol. 2015;126(6):e135–42.Google Scholar
- 68.Hemmatian H, Jalali R, Semeins CM, Hogervorst JMA, van Lenthe GH, Klein-Nulend J, et al. Mechanical loading differentially affects osteocytes in fibulae from lactating mice compared to osteocytes in virgin mice: possible role for lacuna size. Calcif Tissue Int. 2018;103(6):675–85.PubMedPubMedCentralCrossRefGoogle Scholar
- 70.Shea JE, Doody SL, Elsenman PA, Miller SC, editors. Augmentation of bone gains during the anabolic post-lactation recovery period utilizing a rat bipedal stance model. American Society of Bone and Mineral Research Annual Meeting; 2005; Nashville, TN.Google Scholar
- 71.• Tsourdi E, Jahn K, Rauner M, Busse B, Bonewald LF. Physiological and pathological osteocytic osteolysis. J Musculoskelet Neuronal Interact. 2018;18(3):292–303 This paper provided a comprehensive review on the peri-lacunar/canalicular remodeling in physiological and pathological conditions and the current understanding of molecular mechanisms behind this osteocyte function. PubMedPubMedCentralGoogle Scholar
- 76.• Wang B, Lai X, Price C, Thompson WR, Li W, Quabili TR, et al. Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system. J Bone Miner Res. 2014;29(4):878–91 This study linked cellular hydaulic forces (shear and drag) with in vivo bone formation and provided evidence that osteocyte pericellular matrix serves as a flow sensor in the lacunar-canalicular system. PubMedPubMedCentralCrossRefGoogle Scholar
- 77.• Weinbaum S, Cowin SC, Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. 1994;27(3):339–60 This paper established the theoritical framework demonstrating interstitial fluid flow in mechanically loaded bone imparts fluid shear stress on the osteocyte cell process membrane. CrossRefGoogle Scholar
- 89.Li Y, De Bakker CM, Tseng WJ, Zhao H, Parajuli A, Wang L et al. Peri-lacunar/canalicular (PLC) remodeling enhances mechano-sensitivity in rat maternal bone when subjected to estrogen deficiency. American Society of Bone and Mineral Research Annual Meeting; 2018; Montreal, Canada.Google Scholar