Biology subjects

Lambers, F. M.

Publications and source records attributed to Lambers, F. M..

3 recordsLinked to original sources

bioRxiv2026

Differential Adaptation of Osteocyte Lacunar Morphology at Bone (Re)modeling Sites under Mechanical Loading and Pharmacological Therapies in a Mouse Model of Osteoporosis

Postmenopausal osteoporosis is a highly prevalent disease characterized by low bone mass and structural deterioration of bone tissue leading to increased bone fragility and fracture risk. Osteocytes orchestrate local bone (re)modeling and therefore, characterizing their 3D morphological and spatial distribution across distinct (re)modeling microenvironments is essential for understanding the cellular mechanisms underlying divergent tissue-level responses. To address this, we used a 3D-3D multiscale registration framework mapping endpoint osteocyte lacunae onto dynamic, time-lapsed in vivo (re)modeling sites. Ovariectomized 15-week-old mice were subjected to 4 weeks of anabolic parathyroid hormone (PTH) or anti-catabolic bisphosphonate (BIS) treatment as monotreatment or combined with cyclic mechanical loading (ML). Biweekly in vivo micro-computed tomography (micro-CT) to identify (re)modeling sites and endpoint ultra-high resolution (ultra-HR) micro-CT to characterize osteocyte lacunae was performed. Osteocyte lacunae were characterized by lacunar density, volume and sphericity. Our findings showed that physical and pharmacological therapies differentially regulate the osteocyte lacunar network through distinct perilacunar adaptations across functional microenvironments. While BIS stabilizes local lacunar architecture, PTH drives asymmetrical lacunar expansion (increased volume with reduced sphericity) through perilacunar remodeling that supersedes any added ML effects. Crucially, estrogen loss disrupts the natural spatial maturation gradient by inducing rounding of lacunae in newly formed bone. Therapies counteract this disruption, restoring the healthy gradients in lacunar morphometry between spatially distinct microenvironments. Additionally, despite restoring tissue-level bone volume, physical and pharmacological osteoporosis therapies do not fully recover persistent lacunar density deficits. The overall lacunar morphological spatial signatures confirm active osteocytic tuning to endocrine, physical and matrix cues.

bioengineering↗

bioRxiv2024

Mechanical loading potentiates the bone response of anabolic osteoporosis treatments through mechanoregulation at the tissue level

Bones ability to adapt to mechanical demands is governed by mechanoregulation, the process by which cells sense and respond to mechanical stimuli to maintain skeletal integrity. In osteoporosis, increased bone resorption activity leads to structural deterioration and elevated fracture risk. While existing pharmacological therapies aim to restore bone mass to reduce fracture risk, it is unclear how they modulate mechanoregulation, especially when combined with physical interventions. Here, we investigate the joint effects of load-bearing physical and pharmacological treatment in a female mouse model of osteoporosis using longitudinal in vivo micro-computed tomography and computational mechanics. We demonstrate that mechanical loading additively and synergistically enhanced predicted strength, bone volume, and mechanoregulation parameters when combined with anabolic therapies (parathyroid hormone and sclerostin antibody) but not with anti-catabolic treatments (bisphosphonates). Increases in predicted strength are associated with reductions in bone resorption rates, shifts in the (re)modeling thresholds as anticipated by Frost in the mechanostat theory, and the modeling capacity of anabolic pharmacological treatments. These findings underscore the therapeutic potential of combining anabolic pharmacological therapies with load-bearing physical activity, particularly in early treatment phases, to optimize bone adaptation and fracture prevention in osteoporosis management.

bioengineering↗

bioRxiv2018

Bone-Inspired Microarchitectured Materials with Enhanced Fatigue Life

Microarchitectured materials achieve superior mechanical properties through geometry rather than composition 1-4. Although lightweight, high-porosity microarchitectured materials can have high stiffness and strength, stress concentrations within the microstructure can cause flaw intolerance under cyclic loading 5,6, limiting fatigue life. However, it is not known how microarchitecture contributes to fatigue life. Naturally occurring materials can display exceptional mechanical performance and are useful models for the design of microarchitectured materials 7,8. Cancellous bone is a naturally occurring microarchitectured material that often survives decades of habitual cyclic loading without failure. Here we show that resistance to fatigue failure in cancellous bone is sensitive to the proportion of material oriented transverse to applied loads - a 30% increase in density caused by thickening transversely oriented struts increases fatigue life by 10-100 times. This finding is surprising in that transversely oriented struts have negligible effects on axial stiffness, strength and energy absorption. The effects of transversely oriented material on fatigue life are also present in synthetic lattice microstructures. In both cancellous bone and synthetic microarchitectures, the fatigue life can be predicted using the applied cyclic stress after adjustment for apparent stiffness and the proportion of the microstructure oriented transverse to applied loading. In the design of microarchitectured materials, stiffness, strength and energy absorption is often enhanced by aligning the microstructure in a preferred direction. Our findings show that introduction of such anisotropy, by reducing the amount of material oriented transverse to loading, comes at the cost of reduced fatigue life. Fatigue failure of durable devices and components generates substantial economic costs associated with repair and replacement. As advancements in additive manufacturing expand the use of microarchitectured materials to reusable devices including aerospace applications, it is increasingly necessary to balance the need for fatigue life with those of strength and density.

bioengineering↗