Randomized, Placebo-Controlled Pilot Study of Naproxen During Dental Implant Osseointegration.

Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed following the placement of dental implants, but the effects of these drugs on the osseointegration process are poorly understood. We designed a randomized, placebo-controlled pilot study to quantitatively assess the effect of NSAIDs during early implant osseointegration.

Materials And Methods: Subjects receiving a maxillary dental implant were randomized to take naproxen or placebo for 7 days after the surgery.

Regular Nonsteroidal Anti-Inflammatory Drug Use Increases Stress Fracture Risk in the General Population: A Retrospective Case-Control Study.

Previous studies have shown that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased stress fracture risk. This phenomenon has been studied predominantly in high-activity individuals, so data regarding the general population are limited despite the substantial economic and resource burden of stress fracture injuries within the general US population. Furthermore, our preclinical studies demonstrate that regular use of NSAIDs also diminishes the intrinsic ability of bone to resist fracture.

Extrapolation of the Efficacy and Pharmacokinetics of Belimumab to Support its Use in Children with Lupus Nephritis.

Background And Objective: Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, has greater severity in children versus adults. Belimumab is approved for systemic lupus erythematosus treatment in patients aged ≥ 5 years, and for active LN in adults in the European Union, China, Japan and Latin America, and patients aged ≥ 5 years in the USA. Low prevalence of paediatric active LN makes conducting a clinical study within a reasonable period unfeasible.

Medication-related osteonecrosis of the jaw (MRONJ) systemic review: mevalonate pathway mechanisms explored.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but devastating condition caused by bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, anti-angiogenic medications, and disease-modifying antirheumatic drugs. While the clinical spectrum of MRONJ has a wide range, there is a subgroup of patients that do not improve with antibiotics and conservative surgical debridement resulting in pathologic fractures, draining fistulas, and/or osteomyelitis. For the severely affected individuals, the only cure is surgical resection with micro-vascular free flap reconstruction.

Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats.

Digital health technologies and machine learning augment patient reported outcomes to remotely characterise rheumatoid arthritis.

Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients' Apple smartwatch continuously over the study duration.

Patient-centric assessment of rheumatoid arthritis using a smartwatch and bespoke mobile app in a clinical setting.

Rheumatoid arthritis (RA) is a fluctuating progressive disease requiring frequent symptom assessment for appropriate management. Continuous tracking using digital technologies may provide greater insights of a patient's experience. This prospective study assessed the feasibility, reliability, and clinical utility of using novel digital technologies to remotely monitor participants with RA.

Cartilage-specific deficiency represses IGF-1 and enhances osteoarthritis severity in mice.

Objectives: Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of deficiency on the development of post-traumatic and age-associated OA in mice.

Methods: Male cartilage-specific -deficient mice and intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery.

Toll-like receptor 4 signaling in osteoblasts is required for load-induced bone formation in mice.

In mature bone, NGF is produced by osteoblasts following mechanical loading and signals through resident sensory nerves expressing its high affinity receptor, neurotrophic tyrosine kinase receptor type 1 (TrkA), to support bone formation. Here, we investigated whether osteoblastic expression of Toll-like receptor 4 (TLR4), a key receptor in the NF-κB signaling pathway, is required to initiate NGF-TrkA signaling required for load-induced bone formation. Although conditional knockout mice have normal skeletal mass and strength in adulthood, the loss of TLR4 signaling significantly reduced lamellar bone formation following loading.

Approximating scaffold printability utilizing computational methods.

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision.

A Telemedicine Approach for Monitoring COPD: A Prospective Feasibility and Acceptability Cohort Study.

Background: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan.

Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥40 years of age with COPD or asthma-COPD overlap.

Null Mice-a Model for Mineralization Disorder PXE Shows Vertebral Osteopenia Without Enhanced Intervertebral Disc Calcification With Aging.

Chronic low back pain is a highly prevalent health condition intricately linked to intervertebral disc degeneration. One of the prominent features of disc degeneration that is commonly observed with aging is dystrophic calcification. ATP-binding cassette sub-family C member 6 (ABCC6), a presumed ATP efflux transporter, is a key regulator of systemic levels of the mineralization inhibitor pyrophosphate (PPi).

Pilot Study of a Patient Experience with an ELLIPTA Inhaler Electronic Medication Monitor and Associated Integrated System: A Prospective Observational Study Using the COPD Patient-Powered Research Network.

Background: Electronic medication monitors (EMMs) are associated with decreased rescue inhaler use, symptom burden, and increased medication adherence in asthma. However, the use of EMMs in people with chronic obstructive pulmonary disease (COPD) using the ELLIPTA dry powder inhaler has not been studied.

Methods: This was an open-label, single-arm, prospective observational study of EMMs and associated application (app) use over 12 weeks and up to 24 weeks (April-October 2019) in people with self-reported COPD aged ≥40 years enrolled in the COPD Patient-Powered Research Network, using an ELLIPTA inhaler.

Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects.

Leveraging Advancements in Tissue Engineering for Bioprinting Dental Tissues.

3D bioprinting allows biocompatible materials and cells to be deposited in precise locations in three-dimensional space, enabling researchers to surpass the limitations of traditional 2D cell culture and to create innovative therapies. 3D bioprinting is one of the newest tools developed in the field of tissue engineering, which has traditionally utilized a paradigm revolving around scaffolds, cells, and signals. In this review, we discuss how new developments in each of these three research areas relates to bioprinting dental tissues - specifically teeth, periodontal ligament, and alveolar bone.

Function of peripheral nerves in the development and healing of tendon and bone.

Although the functions of the peripheral nervous system in whole body homeostasis and sensation have been understood for many years, recent investigation has uncovered new roles for innervation in the musculoskeletal system. This review centers on advances regarding the function of nerves in the development and repair of two connected tissues: tendon and bone. Innervation in healthy tendons is generally confined to the tendon sheaths, and tendon-bone attachment units are typically aneural.

Circulating inflammatory cytokines alter transcriptional activity within fibrotic tissue of Dupuytren's disease patients.

Dupuytren's disease is a benign fibroproliferative disorder of the hand that results in disabling digital contractures that impair function and diminish the quality of life. The incidence of this disease has been correlated with chronic inflammatory states, but any direct association between inflammatory cytokines and Dupuytren's disease is not known. We hypothesized that advanced fibroproliferation is associated with increased levels of circulating inflammatory cytokines.

The TrkA agonist gambogic amide augments skeletal adaptation to mechanical loading.

The periosteal and endosteal surfaces of mature bone are densely innervated by sensory nerves expressing TrkA, the high-affinity receptor for nerve growth factor (NGF). In previous work, we demonstrated that administration of exogenous NGF significantly increased load-induced bone formation through the activation of Wnt signaling. However, the translational potential of NGF is limited by the induction of substantial mechanical and thermal hyperalgesia in mice and humans.

Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk.

There is mounting evidence suggesting that the commonly used analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), may inhibit new bone formation with physical training and increase risk of stress fractures in physically active populations. Stress fractures are thought to occur when bones are subjected to repetitive mechanical loading, which can lead to a cycle of tissue microdamage, repair, and continued mechanical loading until fracture. Adaptive bone formation, particularly on the periosteal surface of long bones, is a concurrent adaptive response of bone to heightened mechanical loading that can improve the fatigue resistance of the skeletal structure, and therefore may play a critical role in offsetting the risk of stress fracture.

Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion.

There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and its receptor tropomyosin receptor kinase A (TrkA) during tibial fracture repair, finding that they peak during the cartilaginous phase.

A randomised controlled trial of the effect of a connected inhaler system on medication adherence in uncontrolled asthmatic patients.

Suboptimal adherence to maintenance therapy contributes to poor asthma control and exacerbations. This study evaluated the effect of different elements of a connected inhaler system (CIS), comprising clip-on inhaler sensors, a patient-facing app and a healthcare professional (HCP) dashboard, on adherence to asthma maintenance therapy.This was an open-label, parallel-group, 6-month, randomised controlled trial in adults with uncontrolled asthma (asthma control test (ACT) score less than 20) on fixed-dose inhaled corticosteroids/long-acting β-agonist maintenance therapy (n=437).

The Role of Nerves in Skeletal Development, Adaptation, and Aging.

The skeleton is well-innervated, but only recently have the functions of this complex network in bone started to become known. Although our knowledge of skeletal sensory and sympathetic innervation is incomplete, including the specific locations and subtypes of nerves in bone, we are now able to reconcile early studies utilizing denervation models with recent work dissecting the molecular signaling between bone and nerve. In total, sensory innervation functions in bone much as it does elsewhere in the body-to sense and respond to stimuli, including mechanical loading.

Physiological Factors of Female Runners With and Without Stress Fracture Histories: A Pilot Study.

Background: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs.

Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223.

Dose optimization and pharmacokinetic evaluation of α-particle emitting radium-223 dichloride (RaCl) by planar γ-camera or single photon emission computed tomography (SPECT) imaging are hampered by the low photon abundance and injected activities. In this study, we demonstrate SPECT of Ra using phantoms and small animal models. Line phantoms and mice bearing Ra were imaged using a dedicated small animal SPECT by detecting the low-energy photon emissions from Ra.