Robert A. Overman

Salmon Calcitonin Use and Associated Cancer Risk

Objective: To evaluate the strength of evidence supporting a possible association between salmon calcitonin (SCT) use and cancer incidence. Data Sources: Searches of MEDLINE/PubMed, MEDLINE/OVID, and EMBASE (January 1973 to September 2013) were performed using the key search terms salmon calcitonin, humans, nasal calcitonin, and (for EMBASE only) randomized controlled trial. We also performed a manual review of data reviewed by the US Food and Drug Administration (FDA) committee in 2013. Study Selection and Data Extraction: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. Data Synthesis: Intranasal and injectable SCT are FDA-approved for the treatment of postmenopausal osteoporosis. After a safety signal suggested a possible link between SCT use and prostate cancer, the European Medicines Agency and FDA regulatory agencies conducted analyses of SCT randomized controlled trial data to assess cancer-related adverse events and to readdress the approval status of SCT. Eighteen studies were found that compared nasal or oral SCT and placebo. In 15 of the 18 studies, the percentage of malignancy was greater in the SCT arm. The studies varied in quality, outcomes, and length. Most of the studies had poor-quality methods to assess new cancer cases. Conclusions: Current evidence may suggest an association between SCT use and cancer incidence based on studies with poor-quality cancer assessment methods. However, considering the lack of demonstrated efficacy of SCT to reduce fractures, clinicians should consider discontinuing its use for osteoporosis treatment regardless of the FDA’s final approval decision.

United States Adults Meeting 2010 American College of Rheumatology Criteria for Treatment and Prevention of Glucocorticoid‐Induced Osteoporosis

The American College of Rheumatology (ACR) updated its guidelines on the prevention and treatment of glucocorticoid‐induced osteoporosis (GIO) in 2010. An unknown proportion of US adults at risk of fracture due to glucocorticoid use would be recommended antiosteoporosis pharmaceutical (AOP) therapies based on the ACR guidelines.

Baseline age and time to major fracture in younger postmenopausal women

ObjectiveThis study aims to estimate the incidence of first hip or clinical vertebral fracture or major osteoporotic (hip, clinical vertebral, proximal humerus, or wrist) fracture in postmenopausal women undergoing their first bone mineral density (BMD) test before age 65 years. MethodsWe studied 4,068 postmenopausal women, aged 50 to 64 years without hip or clinical vertebral fracture or antifracture treatment at baseline, who were participating in the Women’s Health Initiative BMD cohort study. BMD tests were performed between October 1993 and April 2005, with fracture follow-up through 2012. Outcomes were the time for 1% of women to sustain a hip or clinical vertebral fracture and the time for 3% of women to sustain a major osteoporotic fracture before initiating treatment, adjusting for clinical risk factors and accounting for competing risks. Women without osteoporosis and women with osteoporosis on their first BMD test were analyzed separately. ResultsDuring a maximum of 11.2 years of concurrent BMD and fracture follow-up, the adjusted estimated time for 1% of women to have a hip or clinical vertebral fracture was 12.8 years (95% CI, 8.0-20.4) for women aged 50 to 54 years without baseline osteoporosis, 7.6 years (95% CI, 4.8-12.1) for women aged 60 to 64 years without baseline osteoporosis, and 3.0 years (95% CI, 1.3-7.1) for all women aged 50 to 64 years with baseline osteoporosis. Results for major osteoporotic fracture were similar. ConclusionsBecause of very low rates of major osteoporotic fracture, postmenopausal women aged 50 to 64 years without osteoporosis on their first BMD test are unlikely to benefit from frequent rescreening before age 65 years.

Global Experiential and Didactic Education Opportunities at US Colleges and Schools of Pharmacy

Objective. To assess the characteristics of global experiential and didactic education offerings in the pharmacy curricula. Methods. A 2-stage web-based review of US colleges and schools of pharmacy identified country locations of international advanced pharmacy practice experiences (APPE), globally focused didactic courses, and whether these offerings were interprofessional. Schools were contacted to confirm their offerings and were asked about student participation and demand. Results. Sixty-four percent of responding schools confirmed an international APPE offering in 67 different countries with an average graduating class participation of 6.1%. Forty-seven percent of responding schools confirmed a globally focused course offering with an average graduating class participation of 13.1%. Almost two thirds of international APPEs and a majority of courses were designated as interprofessional. Student demand did not outweigh supply for either. Conclusion. Colleges and schools of pharmacy in the United States are continuing to develop global education opportunities for students in the classroom and throughout the world.

Evaluating Indeterminate Interferon-γ-Release Assay Results in Patients With Chronic Inflammatory Diseases Receiving Immunosuppressive Therapy.

To analyze the rate of indeterminate interferon‐γ–release assay (specifically the QuantiFeron‐TB Gold In‐Tube [QFT‐GIT]) testing for Mycobacterium tuberculosis in patients with chronic inflammatory disease (CID) compared with the general hospital population (GH) and a healthy reference group of hospital employees (HR), and to analyze factors associated with an indeterminate test result.

Time to Osteoporosis and Major Fracture in Older Men. The MrOS Study

INTRODUCTION For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals. METHODS A prospective cohort study of 5,415 community-dwelling men aged ≥65 years without hip or clinical vertebral fracture or antifracture treatment at baseline was conducted. Participants had concurrent BMD and fracture follow-up between 2000 and 2009, and additional fracture follow-up through 2014. Data were analyzed in 2015. Time to incident osteoporosis (lowest T-score ≤ -2.50) for men without baseline osteoporosis, and time to hip or clinical vertebral fracture or major osteoporotic fracture for men without or with baseline osteoporosis, were estimated. RESULTS Nine men (0.2%) with BMD T-scores >-1.50 at baseline developed osteoporosis during follow-up. The adjusted estimated time for 10% to develop osteoporosis was 8.5 (95% CI=6.7, 10.9) years for those with moderate osteopenia (lowest T-score, -1.50 to -1.99) and 2.7 (95% CI=2.1, 3.4) years for those with advanced osteopenia (lowest T-score, -2.00 to -2.49) at baseline. The adjusted times for 3% to develop a first hip or clinical vertebral fracture ranged from 7.1 (95% CI=6.0, 8.3) years in men with baseline T-scores > -1.50 to 1.7 (95% CI=1.0, 3.1) years in men with baseline osteoporosis. CONCLUSIONS Men aged 65 years and older with femoral neck, total hip, and lumbar spine BMD T-scores >-1.50 on a first BMD test were very unlikely to develop osteoporosis during follow-up. Additional BMD testing may be most informative in older men with T-scores ≤-1.50.

Treatment dynamics of bone‐targeting agents among men with bone metastases from prostate cancer in the United States

To examine the dynamics of treatment with 2 bone‐targeting agents (BTAs)—denosumab and zoledronic acid—among men with bone metastases from prostate cancer.

Time to Clinically Relevant Fracture Risk Scores in Postmenopausal Women

BACKGROUND Clinical practice guidelines recommend use of fracture risk scores for screening and pharmacologic treatment decisions. The timing of occurrence of treatment-level (according to 2014 National Osteoporosis Foundation guidelines) or screening-level (according to 2011 US Preventive Services Task Force guidelines) fracture risk scores has not been estimated in postmenopausal women. METHODS We conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores in postmenopausal women aged 50 years and older, prior to receipt of pharmacologic treatment and prior to first hip or clinical vertebral fracture. RESULTS In 54,280 postmenopausal women aged 50 to 64 years without a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of rare incidence of treatment-level scores. In 6096 women who had FRAX scores calculated with bone mineral density, the estimated unadjusted time to treatment-level FRAX ranged from 7.6 years (95% confidence interval [CI], 6.6-8.7) for those aged 65 to 69, to 5.1 years (95% CI, 3.5-7.5) for those aged 75 to 79 at baseline. Of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years. CONCLUSIONS Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.

Use of bone-modifying agents among breast cancer patients with bone metastasis: evidence from oncology practices in the US

Purpose Bone-modifying agents (BMAs) are recommended for women with bone metastasis from breast cancer to prevent skeletal-related events. We examined the usage patterns and identified the factors associated with the use of BMAs (denosumab and intravenous bisphosphonates) among women in the US. Patients and methods Electronic health records from oncology clinics were used to identify women diagnosed with bone metastasis from breast cancer between 2013 and 2014. Patients were excluded if they had recently used a BMA or had concurrent cancer at an additional primary site. The incidence of BMA initiation, interruption, and reinitiation were estimated using competing risk regression models. A generalized linear model was used to estimate risk factors for treatment initiation and interruption. Results There were 589 women diagnosed with bone metastasis from breast cancer. By 1 year, 68% of these patients (95% CI: 64%, 71%) had initiated treatment with a BMA. Denosumab and zoledronic acid were the most commonly used agents, whereas pamidronate was used infrequently. Young women were more likely to initiate a BMA than older women (adjusted risk difference: 6.4 [95% CI: 1.5, 10.9]). Of the 412 patients who initiated a BMA, 46% (95% CI: 41%, 51%) experienced an interruption within 1 year. Seventy-four percent (95% CI: 68%, 79%) of patients who interrupted their treatment had reinitiated therapy within 1 year of interruption. Conclusion The majority of women diagnosed with bone metastasis from breast cancer initiate a BMA within 1 year of diagnosis, but a large proportion, particularly among the elderly, do not use these therapies.

Correction to: Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study

Owing to an oversight by the authors, the acknowledgments were incomplete.