The Role of Exercise in the Treatment of Osteoporosis

The objective of exercise in the treatment of osteoporosis is to improve axial stability through improvement of muscle strength. Therefore, a back extension exercise program specific to one’s musculoskeletal competence and pain can be performed in a sitting position and later advanced to the prone position. When fragility is resolved, back extension is performed against resistance applied to the upper back. To decrease pain and immobility in acute vertebral fracture, use of spinal orthoses become inevitable. Therapeutic exercise should address osteoporosis-related deformities of axial posture, which can increase risk of fall and fracture. Strengthening of the major appendicular muscles decreases fragility. The effect of strengthening exercise is augmented by proper intake of cholecalciferol and calcium. Thus, the role of a therapeutic exercise program is to increase muscle strength safely, decrease immobility-related complications, and prevent fall and fracture. As with pharmacotherapy, therapeutic exercises are individualized.     

Osteoporosis: The Role of the Orthopaedist

Osteoporosis is one of the most prevalent musculoskeletal disorders encountered in orthopaedic practice today. This review provides an update on the pathophysiology of bone metabolism leading to osteoporosis, describes the latest methodology in the diagnostic workup of patients with low bone mass, and summarizes the current status of osteoporosis treatment regimens. The special needs of the osteoporotic fracture patient are also addressed. In general, load-sharing devices and sliding nail-plate constructs are preferred over rigid internal-fixation systems. Prolonged immobilization should be avoided.     

The Role of Risk Communication in the Care of Osteoporosis

Risk assessment and communication of risk are essential components in the care of patients with osteoporosis. The risk of fracture in an untreated patient can be estimated with measurement of bone mineral density, consideration of clinical risk factors, and the use of a validated fracture risk assessment algorithm. When fracture risk is high, pharmacologic therapy to reduce the risk of fracture is indicated, provided no contraindications are present. Initiation, compliance, and persistence with therapy may be enhanced when the patient fully understands the risk of fracture if no treatment is given, as well as the expected benefit and potential risks of treatment. Optimal clinical outcomes with treatment may in part depend on the clinician’s skill in communicating risk with the patient, understanding the patient’s concerns, and reaching a collaborative treatment decision that is medically reasonable and acceptable to the patient.     

The Role of Nanoscale Toughening Mechanisms in Osteoporosis

Strength is the most widely reported parameter with regards to bone failure. However, bone contains pre-existing damage and stress concentration sites, perhaps making measures of fracture toughness more indicative of the resistance of the tissue to withstand fracture. Several toughening mechanisms have been identified in bone, prominently, at the microscale. More recently, nanoscale toughness mechanisms, such as sacrificial-bonds and hidden-length or dilatational band formation, mediated by noncollagenous proteins, have been reported. Absence of specific noncollagenous proteins results in lowered fracture toughness in animal models. Further, roles of several other, putative influencing, factors such as closely bound water, collagen cross-linking and citrate bonds in bone mineral have also been proposed. Yet, it is still not clear if and which mechanisms are hallmarks of osteoporosis disease and how they influence fracture risk. Further insights on the workings of such influencing factors are of high importance for developing complementary diagnostics and therapeutics strategies.     

The Relationship Among Health Literacy, Health Knowledge, and Adherence to Treatment in Patients with Rheumatoid Arthritis

Background

Patients with poor health literacy often lack the knowledge needed to manage their treatment.

Objective

The aim of this cross-sectional study is to determine whether health literacy is a predictor of health knowledge and/or adherence to medication treatment in patients with rheumatoid arthritis.

Method

The study was completed in an urban, outpatient rheumatology setting. Health literacy was measured using the Test of Functional Health Literacy in Adults. The Arthritis Knowledge Questionnaire was modified to measure medication specific health knowledge, and the Morisky Medication Adherence scale was used to measure adherence. Researchers used regression analyses to determine if health literacy was a predicator of knowledge and/or adherence.

Results

Participants (N?=?125) had high mean health literacy scores. The average medication knowledge score was 0.73. Adherence to medication regimen was 0.84. Controlling for patient covariates, health literacy was positively associated with education, race, and age. In adjusted analyses, health literacy was a significant predictor of health knowledge but not adherence. Race, neighborhood income, and confidence with contacting provider about medications were predictors of adherence.

Conclusion

Study findings indicate that health literacy is independently associated with medication knowledge but not medication adherence in patients with rheumatoid arthritis. These results provide useful information for planning initiatives to support individuals with disease self-management.     

The Role of Diet in Osteoporosis Prevention and Management

Diet, a modifiable osteoporosis risk factor, plays an important role in the acquisition and maintenance of bone mass. The influence of diet on bone begins in childhood; even maternal diet can influence bone mass in the offspring. A good general nutritional status and adequate dietary protein, calcium, vitamin D, fruits, and vegetables have a positive influence on bone health, while a high caloric diet and heavy alcohol consumption have been associated with lower bone mass and higher rates of fracture. The evidence for a role of other minerals and vitamins in skeletal health is not as strong, but recent evidence suggests that vitamins C and K might also have an effect on bone.     

Health Technology Assessment in Osteoporosis

We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of health-care resources by decision makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society, with lifetime risks of any fracture of the hip, spine, and forearm of around 40 % for women and 13 % for men. The economic impact is also large; for example, Europe’s six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture-risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision makers in health care on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce health-care resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision makers efficiently allocate health-care resources.     

Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years’ daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 ± 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients. Received: 13 August 2001 / Accepted: 19 February 2002     

Denosumab for the Treatment of Osteoporosis

Being a connective tissue, bone can increase or decrease its mass through the process of remodeling. Using a discovery in the mid-1980s—that tumor necrosis factor (TNF) could dramatically increase formation of osteoclasts (the cells that break down bone)—researchers at Amgen (Thousand Oaks, CA) discovered a TNF-like molecule that regulated bone resorption. Elevations in the expression of this molecule, receptor activator of nuclear factor-κB ligand (RANKL), can cause excessive bone destruction. A blocking antibody to RANKL named denosumab inhibits osteoclast formation and bone degradation. In a large multicenter clinical trial, known as the FREEDOM trial (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months), the effects of denosumab were tested in 60- to 90-year-old women over 3 years. Statistically significant reductions in fracture risk at the vertebral column, hip, and nonvertebral sites were associated with increases in bone mineral density (BMD) and reciprocal decreases in markers of bone resorption. However, the FREEDOM trial did not test the most beneficial use of a resorption blocking drug—to target the rapid bone loss that occurs in late perimenopause and early postmenopause. One adverse effect from denosumab is cellulitis, and research in animals suggests that RANKL/RANK interaction is needed for Langerhans cell (LC) survival in the skin. Further mechanistic and clinical studies on the role of RANKL in the skin are needed.     

The Role of Wnt Signaling and Sclerostin in the Pathogenesis of Glucocorticoid-Induced Osteoporosis

Bone formation is suppressed in glucocorticoid-induced osteoporosis. One of the mechanisms by which glucocorticoids depress bone formation is through their effects on the Wnt/β-catenin signaling pathway, a critical regulator of osteoblastogenesis. Thus, Wnt signaling induces the differentiation of osteoblast precursors toward mature osteoblasts and prevents osteoblast and osteocyte apoptosis. Glucocorticoids increase the expression of Wnt signaling antagonists (sclerostin and Dkk-1) in experimental studies in rodents and cell cultures. However, the scarce data of their effects in humans are somewhat contradictory, probably due to the dose and duration of treatment as well as the characteristics of the patients. A progressive decrease in Dkk-1 serum levels and an increase in circulating sclerostin levels at long-term follow-up have recently been reported in patients treated with high doses of glucocorticoids. This review describes the most recent data on the effects of glucocorticoids on the Wnt signaling pathway, especially on their antagonists, sclerostin and Dkk-1.     

Intermittent Cyclic Tiludronate in the Treatment of Osteoporosis

The objective of the study was to determine the efficacy and safety of tiludronate in the treatment of postmenopausal osteoporosis. Two placebo-controlled, randomized, double-masked, multicenter, cyclical, intermittent, dose-ranging studies including 1805 women with low vertebral bone mineral density and prevalent vertebral fractures and 488 women with low bone mineral density and no prevalent fracture were conducted. Patients were randomized to either tiludronate 50 mg/day, tiludronate 200 mg/day or placebo, given orally for the first 7 days of each month. A supplement of 500 mg elemental calcium was provided daily from day 8 to the end of the month. Both studies demonstrated no statistically or clinically relevant trends in the incidence of adverse effects accross the three treatment groups. However, tiludronate administered at these two doses in a cyclic intermittent regimen was not effective in reducing the incidence of vertebral fractures or increasing spinal bone mineral density. Thus, tiludronate, administered at these doses in a cyclic intermittent regimen, cannot be considered an appropriate treatment of postmenopausal osteoporosis, notwithstanding a high safety profile. Received: 6 July 2000 / Accepted: 25 September 2000