Lactation-Induced Changes in the Volume of Osteocyte Lacunar-Canalicular Space Alter Mechanical Properties in Cortical Bone Tissue

Abstract

Osteocytes can remove and remodel small amounts of their surrounding bone matrix through osteocytic osteolysis, which results in increased volume occupied by lacunar and canalicular space (LCS). It is well established that cortical bone stiffness and strength are strongly and inversely correlated with vascular porosity, but whether changes in LCS volume caused by osteocytic osteolysis are large enough to affect bone mechanical properties is not known. In the current studies we tested the hypotheses that (1) lactation and postlactation recovery in mice alter the elastic modulus of bone tissue, and (2) such local changes in mechanical properties are related predominantly to alterations in lacunar and canalicular volume rather than bone matrix composition. Mechanical testing was performed using microindentation to measure modulus in regions containing solely osteocytes and no vascular porosity. Lactation caused a significant (~13%) reduction in bone tissue-level elastic modulus (p < 0.001). After 1 week postweaning (recovery), bone modulus levels returned to control levels and did not change further after 4 weeks of recovery. LCS porosity tracked inversely with changes in cortical bone modulus. Lacunar and canalicular void space increased 7% and 15% with lactation, respectively (p < 0.05), then returned to control levels at 1 week after weaning. Neither bone mineralization (assessed by high-resolution backscattered scanning electron microscopy) nor mineral/matrix ratio or crystallinity (assessed by Raman microspectroscopy) changed with lactation. Thus, changes in bone mechanical properties induced by lactation and recovery appear to depend predominantly on changes in osteocyte LCS dimensions. Moreover, this study demonstrates that tissue-level cortical bone mechanical properties are rapidly and reversibly modulated by osteocytes in response to physiological challenge. These data point to a hitherto unappreciated role for osteocytes in modulating and maintaining local bone mechanical properties.

The effects of estrogen deficiency on cortical bone microporosity and mineralization

“…While not measured in this study, the presence of a local mineral change at the lacunar-canalicular surface surrounding osteocytes after a drop in estrogen levels would suggest that osteocytes may play a role in mineral mobilization in postmenopausal osteoporosis, similar to what has been shown to occur during lactation [50]. A recent study that investigated the effects of lactation on bone mechanical properties found that an increase in the osteocyte lacunar-canalicular porosity produced a reduction in matrix elastic modulus measured using microindentation [51]. It is possible that canalicular changes previously demonstrated in the rat OVX model [21] could contribute to tissue-level changes that would be evident with microindentation analysis, where the indents are much larger and include lacunar and canalicular void space, but not with the nanoindentation analysis performed in the present study.…”

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

“…A shorter time course or an inducible model would be needed to conclusively address this question. However, our previous studies have shown similar canalicular degeneration within 21 days of glucocorticoid treatment (Fowler et al, 2017) or a week of lactation (unpublished data)(Kaya et al, 2017; Qing et al, 2012; Qing and Bonewald, 2009; Wysolmerski, 2013), thereby indicating that changes in the canalicular network can occur rapidly in a manner that is independent of a maturation defect.…”

“…In this study, PLR mediated changes were observed at osteocyte canaliculi alone. Interestingly, emerging data from our lab and others (Fowler et al, 2017; Kaya et al, 2017; Tang et al, 2012) suggest that remodeling by osteocytes may be spatially defined, such that some circumstances favor remodeling at lacunae, whereas others will promote remodeling around canaliculi. Additional studies will be needed to determine the extent to which this is true.…”

Pamidronate Administration During Pregnancy and Lactation Induces Temporal Preservation of Maternal Bone Mass in a Mouse Model of Osteogenesis Imperfecta

“…Although these changes were modest (16%), it is possible that the lacunar area was higher during the earlier stages of lactation. Prior studies have shown osteocytic perilacunar and canalicular remodeling on the 12th and 14th day of lactation, though our observations were limited to parturition and weaning only. Most importantly, although maternal bone loss was prevented with PAM intervention, PAM showed no effect on osteocyte lacunar remodeling during this crucial period of calcium demand.…”