Response rates for hip, femoral neck, and lumbar spine bone mineral density in patients treated with abaloparatide followed by alendronate: Results from phase 3 ACTIVExtend.

Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor signaling pathway that favors the stimulation of bone formation. Here, we report a prospective, exploratory analysis of bone mineral density (BMD) response rates comparing sequential abaloparatide/alendronate vs placebo/alendronate across the ACTIVE and ACTIVExtend studies. BMD was measured at the lumbar spine, total hip, and femoral neck from the beginning of ACTIVE to the end of ACTIVExtend (18 months of abaloparatide or placebo followed by about 1 month for re-consent, followed by 24 months of alendronate treatment for a total of 43 months). Responders were defined as those patients who had improvements in BMD at 3 anatomic sites-the lumbar spine, total hip, and femoral neck. Three response thresholds, >0%, >3%, and >6%, were evaluated. Five hundred fifty-eight patients in the abaloparatide/alendronate group and 581 patients in the placebo/alendronate group from ACTIVExtend were included in the analysis. At Month 43, a significantly greater proportion of those in the abaloparatide/alendronate group compared with the placebo/alendronate group responded with BMD changes from ACTIVE baseline of >0%, >3%, and >6% at all 3 anatomic sites (p < 0.001 for each comparison). At the>3% threshold, 60.7% (307/506) vs 24.0% (121/505) of patients experienced BMD increases at all 3 sites in the abaloparatide/alendronate vs placebo/alendronate groups, respectively (p < 0.001). A significantly greater proportion of the abaloparatide/alendronate group experienced BMD increases of>0%, >3%, and >6% at each individual anatomic site compared with the placebo/alendronate group at 43 months (p < 0.001). Additionally, at each visit in ACTIVExtend, there was a significantly greater proportion of patients in the abaloparatide/alendronate group above the 3% threshold at each anatomic site compared with the placebo/alendronate group. Results are consistent with the significant BMD response with abaloparatide vs placebo observed in ACTIVE and with the continued fracture risk reduction with sequential abaloparatide/alendronate compared with placebo/alendronate treatment observed in ACTIVE through ACTIVExtend.

DXA Utilization Between 2006 and 2012 in Commercially Insured Younger Postmenopausal Women.

Reimbursement for dual-energy X-ray absorptiometry (DXA) scans in the outpatient setting has declined significantly since 2006. Research through 2011 has suggested reimbursement reductions for DXA scans have corresponded with an overall decreased utilization of DXA. This study updates utilization estimates for DXAs through 2012 in patients with commercial insurance and compares DXA rates before and after reimbursement changes. We evaluated DXA utilization for women aged 50-64 yr from Marketscan Commercial Claims and Encounter database between January 2006 and December 2012 based on CPT codes. We estimated utilization rates per 1000 person years (PY). We also used segmented regression analysis of monthly rates to evaluate the change in utilization rates after a proposed reimbursement reduction in July 2009. In women aged 50-64 yr, 451,656 DXAs were performed in 2006, a rate of 144 DXAs per 1000 PY. This rate increased to 149 DXAs per 1000 PY in 2009 before decreasing to 110 DXAs per 1000 PY or 667,982 scans in 2012. DXA utilization increased by 2.24 per 1000 PY until July 2009 then declined by 12.98 DXAs per 1000 persons, resulting in 37.5 DXAs per PY fewer performed in 2012 compared with 2006. Since July 2009 a significant decline in DXA utilization occurred in a younger postmenopausal commercially insured population. This decline corresponds with a time period of reductions in Medicare DXA reimbursement.

United States adults meeting 2010 American College of Rheumatology criteria for treatment and prevention of glucocorticoid-induced osteoporosis.

OBJECTIVE: 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. METHODS: Using the 2005-2010 National Health and Nutrition Examination Survey (NHANES) data for postmenopausal women (PMW), and men age ≥50 years reporting current glucocorticoid use, we categorized individuals according to ACR criteria for low, medium, and high fracture risk (<10%, ≥10%, and ≥20%, respectively) and provided percentages of treatment recommendations for chronic (≥90 days) medium and all high-risk patients. RESULTS: Glucocorticoids were used by 1.66% of PMW and 1.65% of men age ≥50 years. Of these patients, 0.80% of PMW and 0.45% of men age ≥50 years were at high risk of fracture. A majority of PMW (81.2%) and men age ≥50 years (75.8%) were chronic glucocorticoid users. In patients for whom treatment recommendations could be made, 64.9% of PMW and 51.9% of men age ≥50 years would be recommended therapy, but only 28.4% of PMW and 9.7% of men age ≥50 years reported AOP use. CONCLUSION: Based on the NHANES (2005-2010) data, we estimate glucocorticoid use in >1.5 million US PMW and men age ≥50 years. Treatment would be recommended in at least 50% of this population based on the 2010 ACR guidelines. Self-reported AOP use was documented in <30%, suggesting a treatment gap in the management of GIO in the US before the guideline release.

The Official Positions of the International Society for Clinical Densitometry: vertebral fracture assessment.

Vertebral fracture assessment (VFA) is a low-cost method of accurately identifying individuals who have clinically unrecognized or undocumented vertebral fractures at the time of bone density test. Because prevalent vertebral fractures predict subsequent fractures independent of bone mineral density and other clinical risk factors, their recognition is an important part of strategies to identify those who are at high risk of fracture, so that prevention therapies for those individuals can be implemented. The 2007 Position Development Conference developed detailed guidelines regarding the indications for acquisition of, and interpretation and reporting of densitometric VFA tests. The purpose of the 2013 VFA Task Force was to simplify the indications for VFA yet keep them evidence based. The Task Force reviewed the literature published since the 2007 Position Development Conference and developed prediction models based on 2 large cohort studies (the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study) and the densitometry database of the University of Chicago. Based on these prediction models, indications for VFA were reduced to a simplified set of criteria based on age, historical height loss, use of systemic glucocorticoid therapy, and self-reported but undocumented prior vertebral fracture.

Indications of DXA in women younger than 65 yr and men younger than 70 yr: the 2013 Official Positions.

Dual-energy X-ray absorptiometry (DXA) is the method of choice to assess fracture risk for women 65 yr and older and men 70 yr and older. The 2007 International Society for Clinical Densitometry Official Positions had developed guidelines for assessing bone density in younger women during and after the menopausal transition and in men 50-69 yr and the 2008 National Osteoporosis Foundation (NOF) guidelines recommended testing in postmenopausal women younger than 65 yr and men 50-69 yr only in the presence of clinical risk factors. The purpose of the 2013 DXA Task Force was to reassess the NOF guidelines for ordering DXA in postmenopausal women younger than 65 yr and men 50-69 yr. The Task Force reviewed the literature published since the 2007 Position Development Conference and 2008 NOF, reviewing clinical decision rules such as the Osteoporosis Screening Tool and FRAX and sought to keep recommendations simple to remember and implement. Based on this assessment, the NOF guidelines were endorsed; DXA was recommended in those postmenopausal women younger than 65 yr and men 50-69 yr only in the presence of clinical risk factors for low bone mass, such as low body weight, prior fracture, high-risk medication use, or a disease or condition associated with bone loss.

Recent recommendations on steroid-induced osteoporosis: more targeted, but more complicated.

The latest recommendations for preventing and treating glucocorticoid-induced osteoporosis, published by the American College of Rheumatology (ACR) in 2010, incorporate developments that occurred since the release of its 2001 guidelines, such as new drugs and the World Health Organization's Fracture Risk Assessment Tool, or FRAX. They outline a more targeted approach but have the possible disadvantage of being more complicated and therefore harder to use.

Prevalence of oral glucocorticoid usage in the United States: a general population perspective.

OBJECTIVE: There is little information on oral glucocorticoid use in the general US population. Previously, there have been published estimates of glucocorticoid use in countries outside of the US. This study aimed to estimate the prevalence of glucocorticoid use, duration of use, and concomitant use of antiosteoporosis pharmaceuticals in the US population age ≥20 years. METHODS: Data from 5 cycles (1999-2008) of the National Health and Nutrition Examination Survey (NHANES) were used to provide nationally representative weighted estimates. Oral glucocorticoids and concomitant use of antiosteoporosis pharmaceuticals (bisphosphonates, calcitonin, calcium, hormone replacement therapies, teriparatide, and vitamin D) were analyzed. RESULTS: There were 356 NHANES respondents ages ≥20 years who reported use of an oral glucocorticoid in the combined cycles between 1999 and 2008. The weighted prevalence of oral glucocorticoid use was 1.2% (95% confidence interval [95% CI] 1.1-1.4) from 1999-2008, corresponding to 2,513,259 persons in the US. The mean duration of oral glucocorticoid use was 1,605.7 days (95% CI 1,261.2-1,950.1), and 28.8% (95% CI 22.2-35.4) of oral glucocorticoid users reported use for ≥5 years. Concomitant use of a bisphosphonate was reported by 8.6% (95% CI 5.1-11.7) of oral glucocorticoid users, and 37.9% (95% CI 31.7-44.0) reported usage of any antiosteoporosis pharmaceutical. CONCLUSION: Based on NHANES data from 1999-2008, it is estimated that the prevalence of glucocorticoid use in the US is 1.2%, with a long duration of use and infrequent use of antiosteoporotic medications compared to other estimates.

Absolute fracture risk.

Clinical evaluation of patients with low bone mass attempts to determine which patients should be offered one of the effective therapies for fracture prevention. Current guidelines are primarily based on bone density. Risk factors are used, but their contribution to fracture risk is not easily assessed. The combination of bone density and risk factors can be used to assess absolute fracture risk, the risk of fracture over a period of time expressed as a percent. This model will allow identification of patients who would benefit most from treatment.

The United States rheumatology workforce: supply and demand, 2005-2025.

OBJECTIVE: To develop and apply a model that allows prediction of current and future supply and demand for rheumatology services in the US. METHODS: A supply model was developed using the age and sex distribution of current physicians, retirement and mortality rates, the number of fellowship slots and fill rates, and practice patterns of rheumatologists. A Markov projection model was used to project needs in 5-year increments from 2005 to 2025. RESULTS: The number of rheumatologists for adult patients in the US in 2005 is 4,946. Male and female rheumatologists are equally distributed up to age 44; above age 44, men predominate. The percent of women in adult rheumatology is projected to increase from 30.2% in 2005 to 43.6% in 2025. The mean number of visits per rheumatologist per year is 3,758 for male rheumatologists and 2,800 for female rheumatologists. Assuming rheumatology supply and demand are in equilibrium in 2005, the demand for rheumatologists in 2025 is projected to exceed supply by 2,576 adult and 33 pediatric rheumatologists. The primary factors in the excess demand are an aging population which will increase the number of people with rheumatic disorders, growth in the Gross Domestic Product, and flat rheumatology supply due to fixed numbers entering the workforce and to retirements. The productivity of younger rheumatologists and women, who will make up a greater percentage of the future workforce, may also have important effects on supply. Unknown effects that could influence these projections include technology advances, more efficient practice methods, changes in insurance reimbursements, and shifting lifestyles. Current data suggest that the pediatric rheumatology workforce is experiencing a substantial excess of demand versus supply. CONCLUSION: Based on assessment of supply and demand under current scenarios, the demand for rheumatologists is expected to exceed supply in the coming decades. Strategies for the profession to adapt to this changing health care landscape include increasing the number of fellows each year, utilizing physician assistants and nurse practitioners in greater numbers, and improving practice efficiency.

Successes and failures in improving osteoporosis care after fragility fracture: results of a multiple-site clinical improvement project.

OBJECTIVE: To improve osteoporosis diagnosis and treatment of fragility fracture patient populations because osteoporosis care is provided infrequently to those patients, leaving them vulnerable to further fractures and increasing debility. METHODS: Osteoporosis experts from 11 US health systems participated in a clinical improvement project based on previously described successful osteoporosis care process redesigns. Participants were taught rapid cycle process improvement methods that are widely used in clinical improvement projects, and were supported in their efforts by the program coordinator. Measures of successful process development included establishing reliable referral from orthopedic fracture care to osteoporosis diagnosis and treatment, nurse coordination and monitoring of osteoporosis care, and use of process management software for registering patients and organizing work. RESULTS: Four sites were able to establish these critical referral and osteoporosis management processes. Two sites were partially successful in increasing orthopedic referrals to consultative care, but otherwise continued traditional care processes. Five were unsuccessful due to inability to implement 1 or more of these key process improvements. CONCLUSION: Reliable osteoporosis care for fracture patients is possible if traditional practice processes are replaced with more effective, well-recognized approaches to chronic disease management.

Raloxifene: a selective estrogen-receptor modulator for postmenopausal osteoporosis - a clinical update on efficacy and safety.

Selective estrogen-receptor modulators are molecules with specific estrogen-receptor binding affinity. Each selective estrogen-receptor modulator induces a unique conformation in the ligand-receptor complex, which leads to transcriptional activation and/or inhibition. Raloxifene 60 mg/day, a benzothiophene selective estrogen-receptor modulator, is approved for the prevention and treatment of postmenopausal osteoporosis. This article provides an update on new studies and further analyses of clinical trial data for raloxifene. The Multiple Outcomes of Raloxifene Evaluation (MORE) trial of women with osteoporosis has described the efficacy of raloxifene in decreasing vertebral fracture risk over 4 years. The Continuing Outcomes Relevant to Evista((R)) (CORE) trial, designed to assess the effects of raloxifene on breast cancer prevention, is a 4-year continuation of MORE. The skeletal and cardiovascular effects of raloxifene in the CORE study were similar to those observed in MORE. The relative risk of developing breast cancer was significantly decreased in women treated with raloxifene, compared with placebo, after 4 years in MORE and 8 years in the CORE trial. The incidence of uterine bleeding, endometrial hyperplasia and endometrial cancer was similar between raloxifene and placebo after 8 years of treatment. Raloxifene use is associated with a higher incidence of hot flashes and leg cramps, and an increased risk of venous thromboembolic events.

Risedronate prevents hip fractures, but who should get therapy?

The Hip Intervention Program (HIP) trial establishes that risedronate (Actonel) prevents hip fracture in elderly women with osteoporosis. However, the drug had no statistically significant effect on hip fracture risk in elderly women in whom bone density status was not known. Patients should be selected for bisphosphonate therapy on the basis of low bone density. A history of vertebral fractures increases the risk for hip fractures.