Stuart L. Silverman

Background: Although osteoarthritis (OA) often affects older persons, it has a profound effect on individuals actively employed. Despite reports of reduced productivity among workers with OA, data are limited regarding the impact of OA among workers. The objective of this study was to evaluate the impact of self-rated OA severity on quality of life, healthcare resource utilization, productivity and costs in an employed population relative to employed individuals without OA. Methods: This cross-sectional analysis used data derived from the 2009 National Health and Wellness Survey (NHWS). Multivariable analyses characterized outcomes and costs (direct medical costs and indirect) among workers (full-time, part-time, or self-employed) ≥ 20 years of age who were diagnosed with OA and who self-rated their OA severity as mild, moderate, or severe relative to workers without OA. Evaluated outcomes included productivity, assessed using the Work Productivity and Impairment (WPAI) scale; health-related quality of life, using the SF-12v2 Health Survey; and healthcare resource utilization. Results: 4,876 workers reported being diagnosed with OA (45.0% mild, 45.9% moderate, and 9.1% severe); 34,896 workers comprised the non-OA comparator cohort. There was a greater proportion of females in the OA cohort (55.5% vs 45.6%; P < 0.0001) and more individuals in the 40-64 year and ≥ 65 year age ranges (P < 0.0001). As OA severity increased, workers reported more frequent pain, poorer quality of life, greater use of specific healthcare resources (hospitalizations) and reduced productivity. All outcomes indicated a significantly greater burden among workers with OA relative to those without OA (P < 0.0001). Estimated total annual costs per worker were $9,801 for mild OA, $14,761 for moderate OA, $22,111 for severe OA compared with $7,901 for workers without OA (P < 0.0001). Conclusions: Workers with OA were characterized by significant disease and economic burdens relative to workers without OA that substantially increased with greater self-rated OA severity. Greater levels of OA severity were associated with reductions in quality of life and productivity, and increases in healthcare resource utilization and costs.

Guidelines for osteoporosis treatment are available; however, these guidelines suggest when to treat patients, without specific recommendations on what drugs to prescribe in various situations. Choice of osteoporosis therapy should be individualized based on consideration of the efficacy, safety, cost, convenience (i.e., dosing regimen and delivery), and other non-osteoporosis-related benefits associated with each agent. Bisphosphonates, administered orally or intravenously, should be considered first-line therapy, particularly in older patients, owing to their efficacy across multiple skeletal sites; however, there are potential short- and long-term safety concerns. Selective estrogen receptor modulators should be considered for younger postmenopausal women at greater risk for vertebral than hip fractures or as second-line therapy in women who cannot tolerate first-line therapies. Low-dose hormone therapy may be appropriate as prevention in women with menopausal symptoms at lower fracture risk. Calcitonin, with its relatively benign safety profile, may be appropriate for elderly women who may have difficulty following the complex dosing schedules of oral bisphosphonates. Anabolic therapies such as teriparatide should be considered for high-risk patients. Strontium ranelate (approved outside of North America), with both anabolic and antiresorptive properties, may be appropriate for women who cannot tolerate or are unable to take bisphosphonates. Denosumab is a monoclonal antibody appropriate for women at high fracture risk or who have failed other osteoporosis therapies, and may be considered in patients with renal insufficiency. It will be important to incorporate newer agents (e.g., bazedoxifene, tissue selective estrogen complex) into this individualized treatment paradigm to optimize clinical outcomes in patients with osteoporosis.

In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated. This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years. A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N = 7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers. At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P < 0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (n = 1,324; femoral neck T-score ≤−3.0 and/or ≥1 moderate or severe or ≥2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P = 0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P < 0.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P < 0.05) and was generally safe and well tolerated. The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.

Background: There are no standard criteria for defining or assessing severity of fibromyalgia (FM) as a condition as fibromyalgia is associated with multiple symptom domains. The objective of this study was to evaluate whether patient self-reported severity of FM is associated with severity of pain and sleep interference and the presence of core co-morbidities. Methods: We recruited individuals ≥ 18 years of age with a clinician-confirmed diagnosis of FM ≥ 3 months and a current pain rating >2 on a 0-10 numeric rating scale (NRS). Patients completed a questionnaire by mail in which they self-rated their FM severity (very mild, mild, moderate, and severe), their current pain severity and extent of sleep interference (NRS; mild, 0-3; moderate, 4-6, severe, 7-10), and provided information (yes/no) on the presence of core comorbidities (symptoms of depression, anxiety, sleep problems, back pain, neck pain) and medication use for FM. The core symptoms of FM were stratified to assist with patient characterization. Analysis of variance (ANOVA) was used to explore the relationship between self-reported FM severity and continuous variables (pain severity and sleep interference), and Mantel-Haenszel chi-square analysis was used to evaluate the trend in the proportions of patients reporting use of medications and core symptoms of FM by severity of FM. To complement patient-reported FM severity and to understand physicians' perspectives, a survey was performed among 28 physician specialists (rheumatology, neurology, anesthesiology/pain management, family practice, internal medicine, and psychiatry) to determine what they assessed when evaluating FM severity in clinical practice. Results: The population (N = 129) of FM patients was predominantly female (89.1%), with a mean age of 49.4 ± 11.0 years, and 81.4% reported duration ≥ 2 years. Self-reported FM severity was moderate/severe in 86.0% of patients; mean current pain score was 6.40 ± 2.19 (moderate), and mean sleep interference score was 7.28 ± 2.23 (severe). Greater FM severity was significantly associated with higher levels of current pain and sleep interference (p < 0.0001), the proportion of patients reporting FM medication use (p = 0.0001), and the presence of core comorbidities (p < 0.05). Pain, functional disability, and fatigue severity were ranked as the top three criteria by the highest proportion of physicians when evaluating FM severity. Conclusion: With higher self-reported FM severity, patients have greater pain and sleep interference as well as increased frequency of core comorbidities. Further investigation into understanding FM severity is warranted.

In this 3-yr, randomized, double-blind, placebo- and active-controlled study, healthy postmenopausal women with osteoporosis (55–85 yr of age) were treated with bazedoxifene 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. The primary endpoint was incidence of new vertebral fractures after 36 mo; secondary endpoints included nonvertebral fractures, BMD, and bone turnover markers. Among 6847 subjects in the intent-to-treat population, the incidence of new vertebral fractures was significantly lower (p < 0.05) with bazedoxifene 20 mg (2.3%), bazedoxifene 40 mg (2.5%), and raloxifene 60 mg (2.3%) compared with placebo (4.1%), with relative risk reductions of 42%, 37%, and 42%, respectively. The treatment effect was similar among subjects with or without prevalent vertebral fracture (p = 0.89 for treatment by baseline fracture status interaction). The incidence of nonvertebral fractures with bazedoxifene or raloxifene was not significantly different from placebo. In a posthoc analysis of a subgroup of women at higher fracture risk (femoral neck T-score ≤ –3.0 and/or ≥1 moderate or severe vertebral fracture or multiple mild vertebral fractures; n = 1772), bazedoxifene 20 mg showed a 50% and 44% reduction in nonvertebral fracture risk relative to placebo (p = 0.02) and raloxifene 60 mg (p = 0.05), respectively. Bazedoxifene significantly improved BMD and reduced bone marker levels (p < 0.001 versus placebo). The incidence of vasodilatation, leg cramps, and venous thromboembolic events was higher with bazedoxifene and raloxifene compared with placebo. In conclusion, bazedoxifene significantly reduced the risk of new vertebral fracture in postmenopausal women with osteoporosis and decreased the risk of nonvertebral fracture in subjects at higher fracture risk.

Paget disease of bone is a disorder of unknown etiology involving disturbances in bone remodeling, typically leading to bone pain and other complications such as skeletal deformities, fractures, hearing loss, and neurologic complications. Bisphosphonates (BPs), both oral and intravenous, have improved Paget treatment by reducing and normalizing bone turnover, as measured by biochemical markers and by alleviating symptoms. Six BPs are currently approved by the US Food and Drug Administration (FDA) for the treatment of Paget disease, and each has unique characteristics, such as response rates and requirements for dosage and administration, relevant to clinical outcome. This review provides an overview of these agents—including oral drugs such as alendronate and risedronate, and the intravenous agent zoledronic acid—and briefly discusses other options for managing Paget disease and monitoring treatment efficacy.

Numerous studies have analyzed data from administrative claims databases to determine persistence and compliance with bisphosphonate therapy for osteoporosis; several of these studies have also examined how persistence and compliance with therapy affect fracture outcomes. All of the studies included in this review demonstrated that patients who were persistent or compliant with therapy had a...