Descriptive analysis of concomitant prescription medication patterns from 1999 to 2004 among US women receiving daily or weekly oral bisphosphonate therapy.

BACKGROUND: To improve medication-taking behavior, it is important to identify factors that may contribute to suboptimal compliance and persistence with osteoporosis medications. OBJECTIVE: The purpose of this descriptive analysis was to identify concurrent prescription medication use (number and type) among women receiving daily or weekly oral bisphosphonate therapy. METHODS: Patient prescription data were collected from November 1999 to June 2004 from a US patient claims database accessed through Wolters Kluwer Health (formerly NDC Health), which represents >65 million patients annually. Women aged >or=50 years who were receiving daily or weekly oral bisphosphonate medication during the study months were included. Concomitant medications were defined based on >or=14 days of prescription supply in the same month as bisphosphonate therapy. Data were examined to determine the frequency with which certain drugs and drug classes were prescribed concomitantly with bisphosphonates. Each study month was treated independently to assess concomitant medication use. RESULTS: Over the study period, the number of female bisphosphonate recipients in the database increased from 78,909 to 250,286. At the end of the study, 16.2%, 12.2%, 8.7%, and 19.1% of bisphosphonate recipients were prescribed 3, 4, 5, or >or=6 concomitant medications, respectively. The most commonly prescribed concomitant drug classes were cholesterol reducers, diuretics, beta-blockers, calcium channel blockers, synthetic thyroid hormones, angiotensin-converting enzyme inhibitors, systemic analgesics/anti-inflammatory drugs, and antispasmodics/antisecretory drugs. From July 2001 until the end of the study, the number of concomitant medications was higher for women receiving daily bisphosphonates than for those receiving weekly bisphosphonates, 4.16 versus 3.77 as of June 2004. In addition, the mean number of concomitant medications prescribed increased with age: in the aged 50 to 64 years cohort, the aged 65 to 74 years cohort, and the aged >or=75 years cohort, the mean number was 3.09, 3.62, and 3.97, respectively, as of June 2004. CONCLUSION: This analysis suggests that women prescribed bisphosphonates have a high medication burden, with the majority of patients (56%) taking >or=3 concomitant prescription medications.

HSA: beyond BMD with DXA.

The measurement of bone mineral density is a surrogate for the measurement of bone strength. Bone strength is comprised of many components including, but not limited to bone architecture, geometry, cortical porosity and tissue mineralization density. A new application for dual energy X-ray absorptiometry (DXA), called hip structural or hip strength analysis (HSA), allows the measurement of geometric contributions to bone strength in the proximal femur. With this approach, the cross-sectional area, section modulus and buckling ratio can be quantified. These parameters are measures of strength in axial compression or bending. The limitations of HSA with DXA are primarily those associated with the two-dimensional nature of DXA. Because of the two-dimensional nature of DXA, assumptions must be made regarding the symmetry of the bone cross-sections used in the HSA regions of interest. In one proprietary approach to HSA, an index, called the Femur Strength Index, has been created in an attempt to relate the force of a fall on the greater trochanter to the strength of the proximal femur. Studies using HSA with DXA have demonstrated discordant behaviors between the bone mineral density (BMD) and the section modulus. The geometric parameters are predictive of fracture risk although they do not seem to be better predictors of risk than a conventional measurement of BMD. Various bone active agents have been shown to have desirable effects on these geometric parameters. Direct measurement of these components of bone strength may result in improved fracture risk prediction or therapeutic monitoring. Minimally, a better understanding of the changes in these components of bone strength in disease and during therapy may result from HSA.

Response to therapy with once-weekly alendronate 70 mg compared to once-weekly risedronate 35 mg in the treatment of postmenopausal osteoporosis.

OBJECTIVE: The FACT study (Fosamax Actonel Comparison Trial) was a 1-year-head-to-head trial comparing the efficacy and tolerability of once weekly (DW) alendronate 70 mg and OW risedronate 35 mg for the treatment of postmenopausal osteoporosis. The present analysis was performed to determine the percentage of patients who had changes during the study in BMD and biochemical markers (BCMs) of bone turnover above or below specific cut-off points. A subgroup analysis of upper gastrointestinal (UGI) tolerability was also performed. RESEARCH DESIGN AND METHODS: 1053 postmenopausal women with low BMD were randomized to alendronate 70 mg OW (N = 520) or risedronate 35 mg OW (N = 533). The percentage of patients who had measured BMD gains > or = 3%, and > or = 5% after 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS) was analyzed. The percentage of patients who experienced any bone loss, and those with measured losses of 3% or more at these sites after 12 months, was determined. The percentage of patients achieving reductions in urinary N-telopeptide of type 1 human collagen (NTX) > or = 40%, and serum C-telopeptide of type 1 collagen (CTx) > or = 60%, bone-specific phosphatase (BSAP) > or = 30%, and N terminal propeptide of type 1 procollagen (P1NP) > or = 50% at 3 months and 12 months was also determined. Tolerability, based on adverse experience reporting, was evaluated in a subgroup of patients with history of UGI disorders at baseline. RESULTS: A greater percentage of alendronate- than risedronate-treated patients had measured BMD gains (> or = 0%) (p < 0.05) at all sites at 12 months. Significantly more (p < 0.01) alendronate- than risedronate-treated patients had measured gains in BMD > or = 3% and > or = 5% at the hip trochanter, total hip, and LS spine. Significantly more (p < 0.05) risedronate- than alendronate-treated patients had an apparent loss of BMD (> 0% and > or = 3% loss) at the same sites. After 3 months, significantly (p < 0.001) more alendronate- than risedronate- treated patients achieved predefined reductions in all BCMs. Similar tolerability was demonstrated in both treatment groups, regardless of whether or not patients had a history of UGI disorders at baseline. CONCLUSIONS: Significantly more alendronate- than risedronate-treated patients achieved predefined increases in BMD at 12 months and reductions in BCMs at 3 months. Significantly more risedronate- than alendronate-treated patients were classified as apparent 'non-responders' (i.e. experienced any bone loss) after 12 months of therapy. The tolerability profiles of the two medications were similar.

Patient satisfaction in postmenopausal women treated with a weekly bisphosphonate transitioned to once-monthly ibandronate.

OBJECTIVE: CURRENT, a large, open-label, 6-month, multicenter study, was designed to assess patient satisfaction levels and patient treatment preference after switching from weekly oral bisphosphonates to monthly oral ibandronate for a period of 6 months. METHODS: This study enrolled postmenopausal women who had taken a weekly oral bisphosphonate for at least 3 months for prevention or treatment of osteoporosis or osteopenia at the time of screening. Enrolled patients were switched to 150 mg monthly ibandronate. At baseline and 6 months, patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q), consisting of four domains. Scores were converted to composite satisfaction scores (scale of 0-100). At 6 months, patients completed the Preference Questionnaire. Adverse events were monitored throughout. RESULTS: The intent-to-treat population comprised 1678 patients. OPSAT-Q composite satisfaction scores improved by 9 points by month 6 despite the high mean baseline summary scores (80.1 points). Convenience, overall satisfaction, and quality of life domain scores improved by 15.6, 12, and 9.2 points, respectively. Increased satisfaction was reported by the majority of patients at month 6 (70.4%). Patients who reported stomach upset or suboptimal compliance with prestudy weekly bisphosphonate treatment were more likely to report improved satisfaction (odds ratio [OR] for stomach upset 2.98, 95% CI 1.52, 6.50, p = 0.0026; suboptimal compliance 1.82, 95% CI 1.13-3.04, p = 0.017). After 6 months, 73.6% of patients preferred monthly ibandronate to weekly bisphosphonates. The most frequently occurring adverse events were upper respiratory tract infection (3.2% of patients), dyspepsia (2.5%), fracture (2.4%), arthralgia (2.3%), and gastroesophageal reflux disease, diarrhea, and nausea (2.2% each). CONCLUSIONS: Patients previously using weekly bisphosphonates reported improved satisfaction with monthly ibandronate dosing.

Monitoring changes in bone density.

The relationship between declining bone density and increasing fracture risk is firmly established; the relationship between increasing bone density and decreasing fracture risk is less clear. Because of this, the clinical utility of assessing the therapeutic efficacy of prescription therapies to reduce fracture risk by measuring changes in bone density has been called into question. However, there is substantial clinical trial data to support this approach. Nevertheless, an apparent increase or decrease in the bone density may be misinterpreted without an understanding of the statistical concepts of precision and least significant change. These concepts are not difficult and are of profound clinical importance. If the least significant change is not known, serial measurements of bone density cannot be interpreted. These concepts will be discussed and illustrated, and the rationale for the importance of changes in bone mineral density on therapy will be explored.

Noninvasive assessments of bone strength.

PURPOSE OF REVIEW: Description of new noninvasive technologies or modifications of existing technologies with which individual components of bone strength and bone strength as a whole can be quantified. RECENT FINDINGS: Although bone mineral density has served as an able surrogate for bone strength, it is clear that aspects of bone strength are either not captured or are not discernible within the measurement of bone density. New, noninvasive technologies have been developed to quantify aspects of bone strength such as biomechanical parameters based on geometry and scale and topological parameters of microarchitecture. Finite element modeling utilizes sophisticated mathematical approaches to predict the strength of the whole bone. At present, most of these technologies remain beyond the reach of clinicians, with the exception of hip structural or strength analysis. SUMMARY: Hip strength or structural analysis is widely available because of its incorporation with dual energy X-ray absorptiometry and has been extensively used in clinical research. None of these new approaches has been shown to be superior to the measurement of bone density in the prediction of fracture risk. This fact does not diminish their potential to enhance the understanding of the pathophysiology of fracture and the mechanisms of therapeutic efficacy.

Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both?

Monitoring the efficacy associated with antiresorptive therapy is an intuitive yet integral part of successful osteoporosis management. Although response rates to bisphosphonates in clinical trials--as judged by changes in bone mineral density (BMD)--are generally high, a small percentage of compliant patients do not respond. Accordingly, monitoring may help identify noncompliant patients and allow for other, possibly more successful, therapeutic interventions. Dual energy x-ray absorptiometry is the accepted method of assessing BMD to determine the need for treatment and to monitor its effects. Change in BMD is considered a valid intermediate end point for efficacy of fracture risk reduction. However, clinical trials have shown that the reduction in fracture risk associated with antiresorptive therapy may occur before changes in BMD become apparent. Vertebral fracture benefit is observed even among women who maintain rather than gain BMD during antiresorptive therapy. Clinical trials show that suppression of bone turnover markers after as little as 3 months of therapy is strongly associated with reductions in risk for fracture. Although formal guidelines for monitoring bone turnover markers do not yet exist, there are data to suggest that changes in these markers are valid intermediate endpoints for efficacy of fracture risk reduction that may provide valuable additional data on therapeutic success, particularly early in treatment and before changes in BMD become apparent.

Current controversies in bone densitometry.

In the face of increasing use of all types of bone densitometry in the diagnosis and management of osteoporosis, the limitations of the World Health Organization criteria for the diagnosis of osteoporosis based on bone density measurements have become apparent. Controversy has arisen about whether these criteria should be used for the diagnosis of osteoporosis. Using densitometry to monitor changes in bone density as a measure of therapeutic efficacy has been criticized. It has been suggested that changes in bone density are not surrogates for reduction in fracture risk and that regression to the mean invalidates serial testing. There is both truth and fallacy in these controversies. The resolutions are critical to the role of densitometry in clinical practice.