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Bisphosphonates increase bone mass and reduce fracture risk, but their anti-resorptive action may lead to increases in fatigue microdamage. To investigate how bisphosphonate effects influence changes in bone volume and microdamage in the long term, a strain-adaptive model of bone remodeling and microdamage balance was developed for a continuum-level volume of postmenopausal trabecular bone by invoking...
Conditions of disuse in bed rest patients, as well as microgravity experienced by astronauts are accompanied by reduced mechanical loading, reduced calcium absorption, and lower serum levels of 1,25(OH) 2 D 3 (1,25-D), the active metabolite of vitamin D, all contributing to bone loss. To determine whether 1,25-D or a less calcemic analog, Seocalcitol or EB1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin...
The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) and ligand of receptor activator of NF-κB (RANKL) in human bone is incompletely understood. Most in vitro studies indicate that PTH decreases OPG and increases RANKL production. In primary hyperparathyroidism (PHPT), hypersecretion of PTH leads to enhanced bone resorption and formation with increased risk of fracture...
The purpose of this study was to examine the effect of mineralization on the mechanical properties of embryonic bone rudiments. For this purpose, four-point bending experiments were performed on unmineralized and mineralized embryonic mouse ribs at 16 and 17 days of gestational age. Young's modulus was calculated using force-displacement data from the experiment in combination with finite element...
The association of melanocortin peptide overproduction with enhanced linear growth prompted the current investigation of adrenocorticotropin hormone (ACTH) effects on multipotential chondroprogenitor populations and committed chondrocytes in culture. Two multipotential progenitor populations, rat bone marrow stromal cells (BMSC) and the clonal multipotential cell line RCJ3.1, and two committed chondrocyte...
The measurement of biochemical markers of bone turnover is integral to the diagnosis and management of Paget's disease. Recently, there has been a proliferation of new markers and a move to carry out existing assays on automated platforms. We have assessed the performance of seven currently available markers in 20 patients with Paget's disease undergoing ibandronate therapy (6 or 12 mg) and in nine...
Osteoblast survival is one of the determinants of postmenopausal osteoporosis development. Recent data from animal experiments suggest that cytokines, in particular Fas ligand (FasL), contribute to postmenopausal osteoporosis. We now address the effect of Fas activation in postmenopausal osteoblast survival and the potential modulatory effect of estrogen and raloxifene analog (LY117018).The expression...
Patients with growth hormone deficiency (GHD) have an increased risk of bone fractures. In these patients, the well-described decrease in bone mineral density (BMD) and content (BMC) may, however, not alone explain the increase in fracture rate. Accordingly, the aim of this study was to evaluate collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try...
Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and impair bone repair in both humans and animals. The objective of this study was the detailed histomorphometric evaluation of the influence of the diabetic metabolic state on bone formation and remodeling during bone defect healing depending on the defect size in spontaneously diabetic BB/O(ttawa)K(arlsburg)...
The osteogenic growth peptide (OGP) is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. Recent histologic studies have shown that OGP enhances fracture healing in experimental animals. To assess the effect of systemically administered OGP on the biomechanical and quantitative structural properties of the fracture callus, the present study used an integrated...
It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD =< 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard...
Purpose: To evaluate whether repeated courses of high-dose methylprednisolone (HDMP) affect the lumbar spine bone mineral density (BMD) in children with chronic idiopathic thrombocytopenic purpura (ITP). Materials and methods: This study included 24 patients with chronic ITP and 149 healthy controls. The patients were allocated into three groups according to the number of HDMP courses (30 mg/kg per...
Nanoscale structural analyses of biomineralized materials can frequently help elucidate important structure-function relationships in these complex organic-inorganic composites. Atomic force microscope (AFM) imaging of the exterior surface of trabecular bone reveals a densely woven structure of collagen fibrils, banded with a 67-nm periodicity, and densely packed mineral plates. The mineral plates...
This review concentrates on the physical state of bone mineral at the nanosize range, where it exists as ultrathin, tiny, platelike particles. They have a distinct X-ray pattern, different from that of apatite crystals, but shared by all bone matter irrespective of source or architecture. The main feature of this diffractogram is a broadened undifferentiated and asymmetric peak at about 32 o ...
The selective estrogen receptor modulator (SERM) raloxifene has been shown to reduce the risk of vertebral fracture, but without significant effect on nonvertebral fractures. However, there is a need for SERMs capable of improving mechanical competence and reducing the risk of fractures at multiple skeletal sites, with minimal side effects. We investigated the effects of a new steroidal SERM, HMR-3339,...
In this study, we identified the expression and the regulation of ADAM members (a disintegrin and metalloprotease) at both gene and protein levels during human osteoclast differentiation and activity. Human peripheral blood monocytes (HPBMC) treated with M-CSF and RANKL were used as an in vitro fusion model. In parallel, we used human osteoclastoma (OCL) tumor as a source of mature osteoclasts, and...
Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to study the hierarchical structure of trabecular bone from C57BL/6J (low bone mass) and C3H/HeJ mice (high bone mass). Bone was harvested from two different anatomical locations: femoral metaphysis and L5 vertebra. This investigation focused on three structural scales: the mesostructural (porous network of trabecular...
The mechanical competence of trabecular bone is significantly determined, next to material density, by its three-dimensional (3D) structure. Recent advances in micromagnetic resonance imaging (μ-MRI) acquisition and processing techniques allow the 3D trabecular structure to be analyzed in vivo at peripheral sites such as the distal radius and tibia. The practicality of μ-MRI-based noninvasive virtual...
Primary cultures of bone marrow stromal cells (BMSC) from long bones of young (4-5 months) and old (22-25 months) C57BL/6 male mice were used to study how donor age affects growth and differentiation of osteoblasts and their sensitivity to dexamethasone (DEX). We assessed changes in the number and area of alkaline phosphatase-positive bone-forming osteolastic colonies (CFU-ALP) and in the total number...
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