Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties.

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.

Bone stress injuries.

Bone stress injuries, including stress fractures, are overuse injuries that lead to substantial morbidity in active individuals. These injuries occur when excessive repetitive loads are introduced to a generally normal skeleton. Although the precise mechanisms for bone stress injuries are not completely understood, the prevailing theory is that an imbalance in bone metabolism favours microdamage accumulation over its removal and replacement with new bone via targeted remodelling.

Micropetrosis in hemodialysis patients.

Micropetrosis develops as a result of stagnation of calcium, phosphorus and bone fluid, which appears as highly mineralized bone area in the osteocytic perilacunar/canalicular system regardless of bone turnover of the patients. And microcracks are predisposed to increase in these areas, which leads to increased bone fragility. However, micropetrosis of hemodialysis (HD) patients has not been discussed at all.

AGN1 implant material to treat bone loss: Resorbable implant forms normal bone with and without alendronate in a canine critical size humeral defect model.

Background: Fractures secondary to osteoporosis, particularly those of the hip and spine, are a major public health concern with high social and economic costs. The Local Osteo-Enhancement Procedure (LOEP) is an approach intended to strengthen skeletal areas that are at the highest risk for fracture due to osteoporosis. LOEP involves the implantation of AGN1, a triphasic, calcium-based, osteoconductive material which is then resorbed and replaced by bone.

Effects of anti-resorptive treatment on the material properties of individual canine trabeculae in cyclic tensile tests.

Osteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different.

Skeletal Protection and Promotion of Microbiome Diversity by Dietary Boosting of the Endogenous Antioxidant Response.

There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling.

Fifty years of bisphosphonates: What are their mechanical effects on bone?

After fifty years of experience with several generations of bisphosphonates (BPs), and 25 years after these drugs were approved for use in humans, their mechanical effects on bone are still not fully understood. Certainly, these drugs have transformed the treatment of osteoporosis in both men and women. There is no question that they do prevent fractures related to low bone mass, and there is widespread agreement that they increase strength and stiffness of the vertebrae.

The Importance of Biologically Active Vitamin D for Mineralization by Osteocytes After Parathyroidectomy for Renal Hyperparathyroidism.

Hypomineralized matrix is a factor determining bone mineral density. Increased perilacunar hypomineralized bone area is caused by reduced mineralization by osteocytes. The importance of vitamin D in the mineralization by osteocytes was investigated in hemodialysis patients who underwent total parathyroidectomy (PTX) with immediate autotransplantation of diffuse hyperplastic parathyroid tissue.

Voluntary Chronic Heavy Alcohol Consumption in Male Rhesus Macaques Suppresses Cancellous Bone Formation and Increases Bone Marrow Adiposity.

Background: Chronic heavy alcohol consumption is an established risk factor for bone fracture, but comorbidities associated with alcohol intake may contribute to increased fracture rates in alcohol abusers. To address the specific effects of alcohol on bone, we used a nonhuman primate model and evaluated voluntary alcohol consumption on: (i) global markers of bone turnover in blood and (ii) cancellous bone mass, density, microarchitecture, turnover, and microdamage in lumbar vertebra.

Methods: Following a 4-month induction period, 6-year-old male rhesus macaques (Macaca mulatta, n = 13) voluntarily self-administered water or ethanol (EtOH; 4% w/v) for 22 h/d, 7 d/wk, for a total of 12 months.

Stress concentrations and bone microdamage: John Currey's contributions to understanding the initiation and arrest of cracks in bone.

The microarchitecture of bone tissue presents many features that could act as stress concentrators for the initiation of bone microdamage. This was first identified by John Currey in a seminal paper in 1962 in which he presented the mechanical and biological evidence for stress concentrations at the bone surface, within the bone through the action of stiffness differentials between architectural features including between lamellae, and at the level of the lacunar and canalicular walls. Those early observations set the stage to consider how microscopic damage to bone tissue might affect the properties of bone at a time when most in the scientific community dismissed microcracks in bone as artifact.

Loss of optimizes osteogenic metabolism and secretion to enhance bone quality.

A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor nuclear matrix protein 4 (, , , ) respond to several classes of osteoporosis drugs with enhanced bone formation compared with wild-type (WT) animals. mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation.

Changes in bone matrix properties with aging.

It is well known that bone loss accompanies aging in both men and women and contributes to skeletal fragility in the older population, but changes that occur to the bone tissue matrix itself are less well known. These changes in bone quality aggravate the skeletal fragility associated with loss of bone mass. Bone tissue quality is affected by age-related changes in bone mineral, collagen and its cross-linking profiles, water compartments and even non-collagenous proteins.

Teriparatide Treatment Increases Mineral Content and Volume in Cortical and Trabecular Bone of Iliac Crest: A Comparison of Infrared Imaging With X-Ray-Based Bone Assessment Techniques.

Teriparatide increases bone mass primarily through remodeling of older or damaged bone and abundant replacement with new mineralizing bone. This post hoc analysis investigated whether dual-energy X-ray absorptiometric (DXA) areal bone mineral density (aBMD) measurement adequately reflects changes of mineral and organic matrix content in cortical and trabecular bone. Paired biopsies and aBMD measurements were obtained before and at end of 2 years of teriparatide treatment from postmenopausal women with osteoporosis who were either alendronate pretreated (mean, 57.

Microcrack-associated bone remodeling is rarely observed in biopsies from athletes with medial tibial stress syndrome.

The pathology of medial tibial stress syndrome (MTSS) is unknown. Studies suggest that MTSS is a bony overload injury, but histological evidence is sparse. The presence of microdamage, and its potential association with targeted remodeling, could provide evidence for the pathogenesis of MTSS.

Osteocytic perilacunar/canalicular turnover in hemodialysis patients with high and low serum PTH levels.

Osteocytic perilacunar/canalicular turnover in hemodialysis patients has not yet been reported. Osteocyte lacunae in lamellar bone and woven bone were classified as eroded surface-, osteoid surface-, and quiescent surface-predominant osteocyte lacunae (ES-Lc, OS-Lc, QS-Lc, respectively) in 55 hemodialysis patients with either high- (n = 45) or low- (n = 10) parathyroid hormone levels, and 19 control subjects without chronic kidney disease. We calculated the area and number of ES-Lc, OS-Lc, and QS-Lc.

Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification.

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca /calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice.

Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies.

Improving Combination Osteoporosis Therapy in a Preclinical Model of Heightened Osteoanabolism.

Combining anticatabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Toward the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 because disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anticatabolic results in superior bone acquisition compared with PTH monotherapy.

STING Contributes to Abnormal Bone Formation Induced by Deficiency of DNase II in Mice.

Objective: Cytosolic DNA sensors detect microbial DNA and promote type I interferon (IFN) and proinflammatory cytokine production through the adaptor stimulator of IFN genes (STING) to resolve infection. Endogenous DNA also engages the STING pathway, contributing to autoimmune disease. This study sought to identify the role of STING in regulating bone formation and to define the bone phenotype and its pathophysiologic mechanisms in arthritic mice double deficient in DNase II and IFN-α/β/ω receptor (IFNAR) (DNase II /IFNAR double-knockout [DKO] mice) compared with controls.