Issues in modern bone histomorphometry

This review reports on proceedings of a bone histomorphometry session conducted at the Fortieth International IBMS Sun Valley Skeletal Tissue Biology Workshop held on August 1, 2010. The session was prompted by recent technical problems encountered in conducting histomorphometry on bone biopsies from humans and animals treated with anti-remodeling agents such as bisphosphonates and RANKL antibodies. These agents reduce remodeling substantially, and thus cause problems in calculating bone remodeling dynamics using in vivo fluorochrome labeling. The tissue specimens often contain few or no fluorochrome labels, and thus create statistical and other problems in analyzing variables such as mineral apposition rates, mineralizing surface and bone formation rates. The conference attendees discussed these problems and their resolutions, and the proceedings reported here summarize their discussions and recommendations

Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2 = 0.58), toughness (h2 = 0.64), and BV/TV (h2 = 0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures

Crystal-clear neuronal computing

Induced progressive crystallization in chalcogenide-based materials can be used to closely mimic neuronal functions, opening new paths to neuromorphic computing

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Bone and cartilage in osteoarthritis: is what's best for one good or bad for the other?

The interest in the relationship between articular cartilage and the structural and functional properties of peri-articular bone relates to the intimate contact that exists between these tissues in joints that are susceptible to the development of osteoarthritis (OA). The demonstration in several animal models that osteoporosis and decreased bone tissue modulus leads to an increased propensity for the development of post-traumatic OA is paradoxical in light of the extensive epidemiological literature indicating that individuals with high systemic bone mass, assessed by bone mineral density, are at increased risk for OA. These observations underscore the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the outcomes in patients with OA

Intraarticular location predicts cartilage filling and subchondral bone changes in a chondral defect: A randomized, blind, long-term follow-up trial involving 82 rabbit knees

Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited.Background and purpose: The natural history of, and predictive factors for outcome of cartilage restoration in chondral defects are poorly understood. We investigated the natural history of cartilage filling subchondral bone changes, comparing defects at two locations in the rabbit knee. Animals and methods: In New Zealand rabbits aged 22 weeks, a 4-mm pure chondral defect (ICRS grade 3b) was created in the patella of one knee and in the medial femoral condyle of the other. A stereo microscope was used to optimize the preparation of the defects. The animals were killed 12, 24, and 36 weeks after surgery. Defect filling and the density of subchondral mineralized tissue was estimated using Analysis Pro software on micrographed histological sections. Results: The mean filling of the patellar defects was more than twice that of the medial femoral condylar defects at 24 and 36 weeks of follow-up. There was a statistically significant increase in filling from 24 to 36 weeks after surgery at both locations. The density of subchondral mineralized tissue beneath the defects subsided with time in the patellas, in contrast to the density in the medial femoral condyles, which remained unchanged. Interpretation: The intraarticular location is a predictive factor for spontaneous filling and subchondral bone changes of chondral defects corresponding to ICRS grade 3b. Disregarding location, the spontaneous filling increased with long-term follow-up. This should be considered when evaluating aspects of cartilage restoration

A new approach to comprehensively evaluate the morphological properties of the human femoral head : example of application to osteoarthritic joint

Osteoarthritis affects the morphological properties of the femoral head. The goal of this study was to develop a method to elucidate whether these changes are localised to discrete regions, or if the reported trends in microstructural changes may be identified throughout the subchondral bone of the human femoral head. Whole femoral heads extracted from osteoarthritic (n = 5) and healthy controls (n = 5) underwent microCT imaging 39 μm voxel size. The subchondral bone plate was virtually isolated to evaluate the plate thickness and plate porosity. The trabecular bone region was divided into 37 volumes of interest spatially distributed in the femoral head, and bone morphometric properties were determined in each region. The study showed how the developed approach can be used to study the heterogeneous properties of the human femoral head affected by a disease such as osteoarthritis. As example, in the superior femoral head osteoarthritic specimens exhibited a more heterogeneous micro-architecture, with trends towards thicker cortical bone plate, higher trabecular connectivity density, higher trabecular bone density and thicker structures, something that could only be observed with the newly developed approach. Bone cysts were mostly confined to the postero-lateral quadrants extending from the subchondral region into the mid trabecular region. Nevertheless, in order to generalise these findings, a larger sample size should be analysed in the future. This novel method allowed a comprehensive evaluation of the heterogeneous micro-architectural properties of the human femoral head, highlighting effects of OA in the superior subchondral cortical and trabecular bone. Further investigations on different stages of OA would be needed to identify early changes in the bone

Tibial stress during running following a repeated calf‐raise protocol

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordTibial stress fractures are a problematic injury amongst runners. Increased loading of the tibia has been observed following prolonged weight‐bearing activity and is suggested to be the result of reduced activity of the plantar flexor muscles. The musculature that spans the tibia contributes to bending of the bone and influences the magnitude of stress on the tibia during running. Participant‐specific models of the tibia can be used as a non‐invasive estimate of tibial stress. This study aimed to quantify tibial stress during running using participant‐specific bone geometry and to compare tibial stress before and after a protocol of repeated muscular contractions of the plantar flexor muscle group. Fourteen participants who run recreationally were included in the final analysis of the study. Synchronised force and kinematic data were collected during overground running before and after an exhaustive, weighted calf‐raise protocol. Bending moments and stress at the distal third of the tibia were estimated using beam theory combined with inverse dynamics and musculoskeletal modelling. Bone geometry was obtained from magnetic resonance images. There was no difference in stress at the anterior, posterior, medial or lateral peripheries of the tibia after the calf‐raise protocol compared with before. These findings suggest that an exhaustive, repeated calf‐raise protocol did not alter tibial stress during running