Trabecular bone structural units and their cement lines change with age, bone volume fraction, structure, and strength in female human vertebrae.

A lifetime of successive bone remodeling events leads to trabeculae which are composed of a patchwork of bone structural units (BSUs) called hemi-osteons or trabecular packets. Traditionally, only intact surface BSUs have been studied, which are those that have been created most recently. Accordingly, the complex changes in the size and distribution of BSU throughout the trabeculae have been overlooked.

Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect.

Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway.

Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis.

Breast cancer bone metastases increase fracture risk and are a major cause of morbidity and mortality among women. Upon colonization by tumor cells, the bone microenvironment undergoes profound reprogramming to support cancer progression, which disrupts the balance between osteoclasts and osteoblasts and leads to bone lesions. A deeper understanding of the processes mediating this reprogramming could help develop interventions for treating patients with bone metastases.

Single-cell Transcriptome Analysis Identifies Senescent Osteocytes as Contributors to Bone Destruction in Breast Cancer Metastasis.

Breast cancer bone metastases increase fracture risk and are a major cause of morbidity and mortality among women. Upon colonization by tumor cells, the bone microenvironment undergoes profound reprogramming to support cancer progression that disrupts the balance between osteoclasts and osteoblasts, leading to bone lesions. Whether such reprogramming affects matrix-embedded osteocytes remains poorly understood.

How osteons form: A quantitative hypothesis-testing analysis of cortical pore filling and wall asymmetry.

Osteon morphology provides valuable information about the interplay between different processes involved in bone remodelling. The correct quantitative interpretation of these morphological features is challenging due to the complexity of interactions between osteoblast behaviour, and the evolving geometry of cortical pores during pore closing. We present a combined experimental and mathematical modelling study to provide insights into bone formation mechanisms during cortical bone remodelling based on histological cross-sections of quiescent human osteons and hypothesis-testing analyses.

Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1-84).

In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1-84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1-84) was discontinued.

Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.

Background: Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases.

Osteoprogenitor recruitment and differentiation during intracortical bone remodeling of adolescent humans.

Background: Recruitment and proliferation of osteoprogenitors during the reversal-resorption phase, and their differentiation into mature bone-forming osteoblasts is crucial for initiation of bone formation during bone remodeling. This study investigates the osteoprogenitors' gradual recruitment, proliferation, and differentiation into bone-forming osteoblasts within intracortical remodeling events of healthy adolescent humans.

Methods: The study was conducted on cortical bone specimens from 11 adolescent human controls - patients undergoing surgery due to coxa valga.

Trabecular bone deterioration in a postmenopausal female suffering multiple spontaneous vertebral fractures due to a delayed denosumab injection - A post-treatment re-initiation bone biopsy-based case study.

Background: Denosumab, is a potent anti-resorptive that, increases bone mineral density, and reduces fracture risk in osteoporotic patients. However, several case studies have reported multiple vertebral fractures in patients discontinuing denosumab.

Case Presentation: This case report describes a 64-year-old female with postmenopausal osteoporosis treated with denosumab, who had her 11th injection delayed by 4 months.

Neuronal Sprouting and Reorganization in Bone Tissue Infiltrated by Human Breast Cancer Cells.

Background: Pain is a common complication for patients with metastatic bone disease. Animal models suggest that the pain, in part, is driven by pathological sprouting and reorganization of the nerve fibers innervating the bone. Here, we investigate how these findings translate to humans.

Alendronate prolongs the reversal-resorption phase in human cortical bone remodeling.

Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new bone. Reduced bone formation has been suggested to lead to accumulation of microfractures and contribute to rare side effects in cortical bone such as atypical femur fractures. However, most studies are limited to trabecular bone.

2D size of trabecular bone structure units (BSU) correlate more strongly with 3D architectural parameters than age in human vertebrae.

Bone tissue is continuously remodeled. In trabecular bone, each remodeling transaction forms a microscopic bone structural unit (BSU), also known as a hemiosteon or a trabecular packet, which is bonded to existing tissue by osteopontin-rich cement lines. The size and shape of the BSUs are determined by the size and shape of the resorption cavity, and whether the cavity is potentially over- or under-filled by the subsequent bone formation.

Vitamin E-doped total hip arthroplasty liners show similar head penetration to highly cross-linked polyethylene at five years: a multi-arm randomized controlled trial.

Aims: The most frequent indication for revision surgery in total hip arthroplasty (THA) is aseptic loosening. Aseptic loosening is associated with polyethylene liner wear, and wear may be reduced by using vitamin E-doped liners. The primary objective of this study was to compare proximal femoral head penetration into the liner between a) two cross-linked polyethylene (XLPE) liners (vitamin E-doped (vE-PE)) versus standard XLPE liners, and b) two modular femoral head diameters (32 mm and 36 mm).

Re-thinking the bone remodeling cycle mechanism and the origin of bone loss.

Proper bone remodeling necessarily requires that osteoblasts reconstruct the bone that osteoclasts have resorbed. However, the cellular events connecting resorption to reconstruction have remained poorly known. The consequence is a fragmentary understanding of the remodeling cycle where only the resorption and formation steps are taken into account.

PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression.

The physiological functions of platelet-derived growth factor receptors (PDGFRs) α and β in osteoblast biology and bone metabolism remain to be established. Here, we show that PDGFRA and PDGFRB genes are expressed by osteoblast-lineage canopy and reversal cells in close proximity to PDGFB-expressing osteoclasts within human trabecular bone remodeling units. We also report that, although removal of only one of the two PDGFRs in Osterix-positive cells does not affect bone phenotype, suppression of both PDGFRs in those osteoblast lineage cells increases trabecular bone volume in male mice as well as in female gonad-intact and ovariectomized mice.

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling.

To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23-day lactation period.

The generation of enlarged eroded pores upon existing intracortical canals is a major contributor to endocortical trabecularization.

The gradual conversion of cortical bone into trabecular bone on the endocortical surface contributes substantially to thinning of the cortical bone. The purpose of the present study was to characterize the intracortical canals (3D) and pores (2D) in human fibular bone, to identify the intracortical remodeling events leading to this endocortical trabecularization. The analysis was conducted in fibular diaphyseal bone specimens obtained from 20 patients (6 women and 14 men, age range 41-75 years).

Absence of an osteopetrosis phenotype in IKBKG (NEMO) mutation-positive women: A case-control study.

Background: NF-κB essential modulator (NEMO), encoded by IKBKG, is necessary for activation of the ubiquitous transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Animal studies suggest NEMO is required for NF-κB mediated bone homeostasis, but this has not been thoroughly studied in humans. IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency.

Understanding age-induced cortical porosity in women: Is a negative BMU balance in quiescent osteons a major contributor?

Cortical bone is remodeled by intracortical basic multicellular units (BMUs), whose end result can be observed as quiescent osteons in histological sections. These osteons offer a unique opportunity to investigate the BMU balance between the magnitude of bone resorption and subsequent bone formation at the BMU level. Our main objective was to investigate whether the latter parameters change between defined categories of osteons and with age, and to which extend these changes contribute to age-induced cortical porosity.

Intracortical Bone Mechanics Are Related to Pore Morphology and Remodeling in Human Bone.

During aging and in osteoporosis, cortical bone becomes more porous, making it more fragile and susceptible to fractures. The aim of this study was to investigate the intracortical compression- induced strain energy distribution, and determine whether intracortical pores associated with high strain energy density (SED) in the surrounding bone matrix have a different morphology and distribution, as well as different remodeling characteristics than matrix with normal SED. Fibular diaphyseal specimens from 20 patients undergoing a jaw reconstruction (age range 41 to 75 years; 14 men and 6 women) were studied.

Understanding Age-Induced Cortical Porosity in Women: The Accumulation and Coalescence of Eroded Cavities Upon Existing Intracortical Canals Is the Main Contributor.

Intracortical bone remodeling normally ensures maintenance of the cortical bone matrix and strength, but during aging, this remodeling generates excessive porosity. The mechanism behind the age-induced cortical porosity is poorly understood and addressed in the present study. This study consists of a histomorphometric analysis of sections of iliac bone specimens from 35 women (age 16-78 years).

Effects of substitute coated with hyaluronic acid or poly-lactic acid on implant fixation: Experimental study in ovariectomized and glucocorticoid-treated sheep.

Investigated in healthy animal models, hyaluronic acid (HyA) and poly- -lactic acid (PDLLA) demonstrate osteoconductive properties when coated onto hydroxyapatite (HA) and β-tricalcium phosphate (βTCP) scaffolds. In this study, we examined the efficacy of HA/βTCP granules coated with HyA or PDLLA on implant fixation when applied as graft materials in 2-mm size defects created in the femur condyles of ovariectomized (OVX) glucocorticoid-treated (GC) sheep. Titanium alloys were inserted into the femur condyles of OVX and GC-treated sheep, and the concentric gaps were filled with either allograft obtained from a healthy donor sheep (control), pure HA/βTCP, HA/βTCP-HyA or HA/βTCP-PDLLA.