Telemedicine delivery of patient education in remote Ontario communities: feasibility of an Advanced Clinician Practitioner in Arthritis Care (ACPAC)-led inflammatory arthritis education program.

Objective: Telemedicine-based approaches to health care service delivery improve access to care. It was recognized that adults with inflammatory arthritis (IA) living in remote areas had limited access to patient education and could benefit from the 1-day Prescription for Education (RxEd) program. The program was delivered by extended role practitioners with advanced training in arthritis care.

Symptom Resolution and Patient-Perceived Recovery Following Ankle Arthroplasty and Arthrodesis.

Background: Patients' perception of outcomes is not always defined by the absence of limitations/symptoms (resolution), but can also be characterized by behavioral adaptation and cognitive coping arising in cases with residual deficits. Patient-reported outcome measures (PROs) are designed to measure levels of function or symptoms, largely missing whether patients are coping with ongoing limitations. This study aimed to broaden the conventional definition of a "satisfactory" outcome following ankle reconstruction by comparing patient-reported outcomes of patients with and without residual symptoms and limitations.

A prospective comparison of telemedicine versus in-person delivery of an interprofessional education program for adults with inflammatory arthritis.

Introduction We evaluated two modes of delivery of an inflammatory arthritis education program ("Prescription for Education" (RxEd)) in improving arthritis self-efficacy and other secondary outcomes. Methods We used a non-randomized, pre-post design to compare videoconferencing (R, remote using telemedicine) versus local (I, in-person) delivery of the program. Data were collected at baseline (T), immediately following RxEd (T), and at six months (T).

Osteoprotegerin is an effective countermeasure for spaceflight-induced bone loss in mice.

Bone loss associated with microgravity exposure poses a significant barrier to long-duration spaceflight. Osteoprotegerin-Fc (OPG-Fc) is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that causes sustained inhibition of bone resorption after a single subcutaneous injection. We tested the ability of OPG-Fc to preserve bone mass during 12 days of spaceflight (SF).

The patient perspective: arthritis care provided by Advanced Clinician Practitioner in Arthritis Care program-trained clinicians.

Objective: To assess patient satisfaction with the arthritis care services provided by graduates of the Advanced Clinician Practitioner in Arthritis Care (ACPAC) program.

Materials And Methods: This was a cross-sectional evaluation using a self-report questionnaire for data collection. Participants completed the Patient-Doctor Interaction Scale, modified to capture patient-practitioner interactions.

Reliability and validity of 6 measures of pain, function, and disability for ankle arthroplasty and arthrodesis.

Background: Patient-reported outcome measures are increasingly used evaluating clinical care. Many measures used to assess operative hindfoot interventions vary in content, and some have not been psychometrically validated in this population. The purpose of this study was to compare measurement properties of 6 lower-extremity patient-reported outcome measures, and to evaluate their reliability and validity in light of patients' preferences.

Progressive increases in bone mass and bone strength in an ovariectomized rat model of osteoporosis after 26 weeks of treatment with a sclerostin antibody.

The effects of up to 26 weeks of sclerostin antibody (Scl-Ab) treatment were investigated in ovariectomized (OVX) rats. Two months after surgery, 6-month-old osteopenic OVX rats were treated with vehicle or Scl-Ab (25 mg/kg, sc, one time per week) for 6, 12, or 26 weeks. In vivo dual-energy x-ray absorptiometry analysis demonstrated that the bone mineral density of lumbar vertebrae and femur-tibia increased progressively through 26 weeks of Scl-Ab treatment along with progressive increases in trabecular and cortical bone mass and bone strength at multiple sites.

System integration and clinical utilization of the Advanced Clinician Practitioner in Arthritis Care (ACPAC) Program-Trained Extended Role Practitioners in Ontario: a two-year, system-level evaluation.

Background: The Advanced Clinician Practitioner in Arthritis Care (ACPAC) program was developed in 2005 to prepare experienced physical and occupational therapists to function as extended role practitioners (ERPs) within models of arthritis care across Ontario, Canada.

Purpose: To examine the system-level integration and clinical utilization of the ACPAC program-trained ERP.

Method: A longitudinal survey was administered to all ACPAC graduates over a two-year period (n=30).

Evaluation of perceived collaborative behaviour amongst stakeholders and clinicians of a continuing education programme in arthritis care.

Successful implementation of new extended practice roles which transcend conventional boundaries of practice entails strong collaboration with other healthcare providers. This study describes interprofessional collaborative behaviour perceived by advanced clinician practitioner in arthritis care (ACPAC) graduates at 1 year beyond training, and relevant stakeholders, across urban, community and remote clinical settings in Canada. A mixed-method approach involved a quantitative (survey) and qualitative (focus group/interview) evaluation issued across a 4-month period.

The ability of outcome questionnaires to capture patient concerns following ankle reconstruction.

Background: The objective of this study was to compare questions from outcome questionnaires with items generated by preoperative and postoperative ankle reconstruction patients (using the open-ended questions of self-reported Patient-Specific Index [PASI]) to determine whether existing questionnaires address patients' concerns.

Methods: Patients (n = 142) completed the PASI. Questions from 6 standardized questionnaires (American Academy of Orthopaedic Surgeons Foot and Ankle Questionnaire [AAOS], patient-reported portion of the American Orthopaedic Foot and Ankle Society Clinical Rating System Ankle-Hindfoot Scale [AOFAS], Foot Function Index [FFI], Lower Extremity Functional Scale [LEFS], Short Musculoskeletal Function Assessment [SMFA], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and PASI were matched by 3 reviewers to corresponding categories in the International Classification of Functioning, Disability and Health (ICF).

Sclerostin is expressed in articular cartilage but loss or inhibition does not affect cartilage remodeling during aging or following mechanical injury.

Objective: Sclerostin plays a major role in regulating skeletal bone mass, but its effects in articular cartilage are not known. The purpose of this study was to determine whether genetic loss or pharmacologic inhibition of sclerostin has an impact on knee joint articular cartilage.

Methods: Expression of sclerostin was determined in articular cartilage and bone tissue obtained from mice, rats, and human subjects, including patients with knee osteoarthritis (OA).

Prescription for education: development, evaluation, and implementation of a successful interprofessional education program for adults with inflammatory arthritis.

Objective: To assess the feasibility of recruitment and standardize care delivery for an interprofessional program for inflammatory arthritis education (Prescription for Education, or RxEd), and to explore outcomes relevant to arthritis patient education.

Methods: A patient-based needs assessment and ongoing patient feedback guided program development. An interprofessional team was involved in developing program content and delivering and adapting the program to patient needs.

Increased bone formation and bone mass induced by sclerostin antibody is not affected by pretreatment or cotreatment with alendronate in osteopenic, ovariectomized rats.

Clinical studies have revealed a blunting of the bone anabolic effects of parathyroid hormone treatment in osteoporotic patients in the setting of pre- or cotreatment with the antiresorptive agent alendronate (ALN). Sclerostin monoclonal antibody (Scl-Ab) is currently under clinical investigation as a new potential anabolic therapy for postmenopausal osteoporosis. The purpose of these experiments was to examine the influence of pretreatment or cotreatment with ALN on the bone anabolic actions of Scl-Ab in ovariectomized (OVX) rats.

Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats.

The purpose of this study was to evaluate the effects of sclerostin inhibition by treatment with a sclerostin antibody (Scl-AbII) on bone formation, bone mass, and bone strength in an aged, gonad-intact male rat model. Sixteen-month-old male Sprague-Dawley rats were injected subcutaneously with vehicle or Scl-AbII at 5 or 25 mg/kg twice per week for 5 weeks (9-10/group). In vivo dual-energy X-ray absorptiometry (DXA) analysis showed that there was a marked increase in areal bone mineral density of the lumbar vertebrae (L(1) to L(5) ) and long bones (femur and tibia) in both the 5 and 25 mg/kg Scl-AbII-treated groups compared with baseline or vehicle controls at 3 and 5 weeks after treatment.

Increased RANK ligand in bone marrow of orchiectomized rats and prevention of their bone loss by the RANK ligand inhibitor osteoprotegerin.

Orchiectomized (ORX) rats were used to examine the extent to which their increased bone resorption and decreased bone density might relate to increases in RANKL, an essential cytokine for bone resorption. Serum testosterone declined by >95% in ORX rats 1 and 2 weeks after surgery (p<0.05 versus sham controls), with no observed changes in serum RANKL.

One year of transgenic overexpression of osteoprotegerin in rats suppressed bone resorption and increased vertebral bone volume, density, and strength.

RANKL is an essential mediator of bone resorption, and its activity is inhibited by osteoprotegerin (OPG). Transgenic (Tg) rats were engineered to continuously overexpress OPG to study the effects of continuous long-term RANKL inhibition on bone volume, density, and strength. Lumbar vertebrae, femurs, and blood were obtained from 1-yr-old female OPG-Tg rats (n = 32) and from age-matched wildtype (WT) controls (n = 23).

Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis.

Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL.

RANKL is a TNF family member that mediates osteoclast formation, activation, and survival by activating RANK. The proresorptive effects of RANKL are prevented by binding to its soluble inhibitor osteoprotegerin (OPG). Recombinant human OPG-Fc recognizes RANKL from multiple species and reduced bone resorption and increased bone volume, density, and strength in a number of rodent models of bone disease.

RANKL inhibition with osteoprotegerin increases bone strength by improving cortical and trabecular bone architecture in ovariectomized rats.

Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats.

Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength.

Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone.

Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone.

Unlabelled: Skeletal anabolism with PTH is achieved through daily injections that result in brief exposure to the peptide. We hypothesized that similar anabolic effects could be achieved with less frequent but more sustained exposures to PTH. A PTH-Fc fusion protein with a longer half-life than PTH(1-34) increased cortical and cancellous BMD and bone strength with once- or twice-weekly injections.

The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy (HHM) is mediated primarily by skeletal and renal responses to tumor-derived PTHrP. PTHrP mobilizes calcium from bone by inducing the expression of receptor activator for nuclear factor-kappaB ligand (RANKL), a protein that is essential for osteoclast formation, activation, and survival. RANKL does not influence renal calcium reabsorption, so RANKL inhibition is a rational approach to selectively block, and thereby reveal, the relative contribution of bone calcium to HHM.

Sustained antiresorptive effects after a single treatment with human recombinant osteoprotegerin (OPG): a pharmacodynamic and pharmacokinetic analysis in rats.

Osteoprotegerin (OPG) is a naturally occurring negative regulator of osteoclast differentiation, activation, and survival. We created a recombinant form of human OPG (rhOPG), with a sustained serum half-life, to achieve prolonged antiresorptive activity. This study describes the rapid and sustained antiresorptive effects that are achieved with a single treatment with rhOPG.