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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

Objective

To evaluate adherence to drug therapy among new users of zoledronate and intravenous (IV) ibandronate among US Medicare enrollees.

Methods

We used data from the Medicare 5% random sample to evaluate new users of IV zoledronate and IV ibandronate with continuous Part A and Part B fee-for-service coverage. The outcome was adherence as quantified by the proportion of days covered (PDC) measured continuously and dichotomously (≥80%). Followup time extended from 18–27 months for all individuals. Factors associated with low adherence to zoledronate were evaluated with logistic regression.

Results

We identified 775 new users of zoledronate and 846 new users of IV ibandronate. For both drugs, 30–48% of the first infusions were given in an outpatient infusion center, not in a physician's office. The mean PDC for zoledronate users was 82%, which was greater than the mean PDC for the IV ibandronate users (58–62% depending on the time period; P < 0.0001). Approximately 30% of zoledronate users did not receive a second infusion. Factors associated with low adherence to zoledronate included older age and receipt of the first infusion in an outpatient infusion center rather than a physician's office.

Conclusion

Less frequently dosed IV bisphosphonates have not resolved the problem of suboptimal adherence with prescription osteoporosis medications. Interventions continue to be warranted to improve long-term adherence to osteoporosis treatments.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

Numerous studies have demonstrated poor adherence to treatment with oral bisphosphonates (1–3), and within the first year after starting therapy, up to one-half or more patients will discontinue therapy. As might be expected, poor adherence has been shown to compromise the antifracture benefit expected with osteoporosis medications (4–6). Besides bisphosphonates, low adherence has also been reported with teriparatide (7), a once-daily injectable medication, despite parenteral administration, which should circumvent the gastrointestinal side effects that are associated with oral bisphosphonate therapy (8). This finding is especially notable given that patients treated with teriparatide are likely to have more severe osteoporosis than patients using oral bisphosphonates and therefore might be more motivated to be adherent to treatment.

The relevance of poor adherence to osteoporosis medications is underscored by the high prevalence, morbidity, and mortality associated with osteoporosis and resulting fractures. In the US, ∼44 million women and men age ≥50 years are estimated to have osteoporosis or low bone mass, accounting for ∼55% of people age ≥50 years (9). Among individuals age ≥65 years, estimates suggest that ∼30% of individuals have osteoporosis and/or a prior fracture (10). A US study using data from 2001–2008 suggested that treatment with oral bisphosphonates prevented >144,000 fractures among all US women age ≥45 years (11). This figure was based upon the medication-related fracture risk reduction observed for the 43% of patients with high adherence (≥80%), an attenuated fracture benefit for the additional 20% of patients with lower adherence (50–79%), and no benefitfor patients that were <50% adherent. Based upon these results, the total number of fractures prevented represented only slightly more than one-half of the number of fractures that could have been prevented if the patients had been more adherent to their prescribed oral bisphosphonates. Improving the problem of nonadherence to osteoporosis therapies would therefore yield a demonstrable public health impact.

Several strategies and interventions to improve adherence to osteoporosis medications have demonstrated at best only modest improvements (12). Therefore, the need for finding new solutions to improve adherence remains. One potential solution to poor adherence is the use of less frequently dosed medications. For example, use of weekly oral bisphosphonates has sometimes been shown to be associated with somewhat better (albeit still poor) adherence compared to daily oral bisphosphonates (13–16). For osteoporosis, intravenous (IV) bisphosphonates can be dosed once every 3 months (IV ibandronate) or every 12 months (zoledronate). At least in theory, adherence to these therapies might be better since they are given by a provider who can detect nonadherence when the patient fails to come back for retreatment. Additionally, parenteral administration may minimize some side effects (e.g., gastrointestinal upset) and avoid the complex instructions required for taking oral bisphosphonates properly.

In light of the limited understanding regarding the adherence to therapy among patients initiating IV bisphosphonates, we examined patterns of use and the frequency of retreatment of these agents for US Medicare enrollees initiating these therapies. We hypothesized that adherence would be better with IV zoledronate compared to IV ibandronate, perhaps based upon the need for less frequent dosing. We also identified factors associated with low versus high adherence with IV zoledronate to specifically evaluate whether the setting in which the initial infusion was given (i.e., a physician's office or a hospital infusion center) was associated with adherence.

Significance & Innovations

  • While substantial research has shown that adherence to oral bisphosphonate therapy is poor, less frequently dosed parenteral osteoporosis medications might yield improved adherence due to more convenient dosing, avoidance of gastrointestinal side effects, and more direct control of administration by health care providers. However, this possibility is largely unexplored.

  • Using a national random sample of Medicare beneficiaries, we studied adherence at 18 months and beyond to the intravenous (IV) bisphosphonates zoledronate and ibandronate. We found that the mean adherence to IV zoledronate was 82%, which was significantly higher than the mean adherence to IV ibandronate (∼60%; P < 0.0001). Approximately 30% of IV zoledronate users received only a single infusion.

  • A key factor associated with low adherence was administration of the medication in an outpatient hospital center rather than in a rheumatologist's, endocrinologist's, or internal medicine physician's office.

  • Despite somewhat better adherence to IV bisphosphonates compared to prior literature reporting adherence to oral bisphosphonates, less frequent parenterally dosed agents have not solved problems of low adherence to osteoporosis therapies.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

Data sources and patient eligibility.

After institutional review board approval, the nationally representative 5% random sample of Medicare data from the Centers for Medicare and Medicaid Services (CMS) from 2005–2009 was used to identify individuals receiving the IV bisphosphonates ibandronate or zoledronate. Patients were required to be enrolled in fee-for-service Medicare with Part A and Part B coverage during a 12-month baseline period prior to the first initiation of the IV bisphosphonate, defined as the index date, and had to retain this coverage throughout followup, which extended for ≥18 months after the index date. The baseline period was used to assess demographics and covariates of interest and to confirm that the patient had not used any IV bisphosphonates prior to the index date to fulfill a new user requirement (17). Covariates included age, sex, geographic region, comorbidities of high interest, location of the first infusion (i.e., hospital infusion center versus physician's office), prior dual x-ray absorptiometry, prior osteoporosis drug use, and oral glucocorticoids. Patients with a diagnosis of Paget's disease of bone (International Classification of Diseases, Ninth Revision code 731.0) during the baseline period were excluded. Patients were required to be covered by the Medicare Part D outpatient drug benefit during at least part of the baseline period, depending on when they started IV bisphosphonate therapy (see below).

Identifying IV bisphosphonate users.

IV ibandronate and zoledronate were first commercially available for the treatment of osteoporosis in May 2006 and August 2007, respectively. Use of these agents in the CMS data was identified based on their permanent Healthcare Common Procedure Coding System (HCPCS) codes (J1740 and J3488 for IV ibandronate and zoledronate, respectively). The permanent HCPCS code for zoledronate used for osteoporosis is distinct from the HCPCS code used for zoledronate when given for the treatment of skeletal-related events associated with malignancy (J3487). Because parenteral medications are not assigned a permanent HCPCS code until after the product is approved, early use of the IV bisphosphonates was identified based upon use of the nonspecific HCPCS codes (J3490) coupled with osteoporosis diagnosis codes (e.g., 733.01), units dispensed (5 units for zoledronate, 3 units for ibandronate), and the billed costs for the infusion.

Patients were assigned to 1 of 3 mutually exclusive cohorts based upon the first IV bisphosphonate that they started and the calendar month in which they initiated therapy. The patient accrual periods for the ibandronate cohorts were matched to the same duration (1 year) of the accrual period for the zoledronate users as follows: zoledronate users who initiated therapy from September 13, 2007 to September 12, 2008; ibandronate users who initiated therapy in the corresponding period of calendar time (September 13, 2007 to September 12, 2008; comparison group 1); and the ibandronate users who initiated therapy from May 1, 2006 to April 30, 2007, the first year that ibandronate was available (comparison group 2). For the zoledronate cohort and comparison group 1, Part D coverage was required for the entire 12-month baseline period. For comparison group 2, patients were required to have Part D medication coverage in the last 4 months of the baseline period (January 2006 to April 2006). Since the Medicare Part D pharmacy benefit first began in the US in January 2006, no additional outpatient medication data were available for Medicare beneficiaries prior to January 2006.

Adherence assessment.

On the date of each IV ibandronate infusion, patients were assigned to 3 months of exposure; for zoledronate, patients were assigned to 12 months of exposure. The primary outcome of interest of the analysis was adherence, defined as the proportion of days covered (PDC), which is similar to a medication possession ratio (18). The PDC was expressed as a proportion, computed by summing the number of days the patient was exposed to the medication, beginning with the first infusion and extending to the end of followup, and dividing by the amount of followup time. For patients who initiated zoledronate in September 2007, up to 27 months of followup time was available in the data set. For comparability, followup for both ibandronate comparison cohorts was therefore truncated at a maximum of 27 months.

The PDC was capped at 100% and was assessed beginning on the date of the first IV zoledronate or first IV ibandronate infusion given, which defined the index date. Patients were allowed to switch between IV bisphosphonates and still be considered adherent to IV bisphosphonate treatment. Since each calendar day was either treated as exposed or not exposed to IV bisphosphonates, overlapping days of exposure due to an early infusion of the same medication or switching to the other IV bisphosphonate did not affect the PDC. Switching from an IV bisphosphonate to an oral bisphosphonate or another osteoporosis medication did not satisfy the definition of adherence or affect the PDC calculation but was examined descriptively.

Statistical analysis.

The PDC was plotted as a probability density function. Chi-square tests were used to compare high adherence (PDC ≥80%) both at 18 months and using all of the followup data between the zoledronate users and IV ibandronate users. Given that the PDC was non–normally distributed, Wilcoxon's rank sum tests were used to compare the PDC as a continuous measure between groups. Multivariable logistic regression was used to identify factors associated with low adherence to zoledronate (defined as <80%, following prior conventions of studies in the literature [4, 5, 11]). The main focus of this analysis was whether patients who received their first zoledronate infusion in a physician's office (rather than at an outpatient hospital–based infusion center) had better adherence. Other factors of interest were determined a priori and included age, race, prior osteoporosis therapy (categorized mutually exclusively as recent use [any prescription for an oral bisphosphonate, calcitonin, raloxifene, or teriparatide within the last 4 months], remote use [any of these prescriptions given 5–12 months before the index date], or neither), the specialty of the physician administering the infusion (relevant only for infusions given in a physician's office), and oral glucocorticoid use. All analyses were conducted using SAS, version 9.2 (SAS Institute).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

We identified 775 new users of IV zoledronate between September 13, 2007 and September 12, 2008, 275 new users of IV ibandronate who initiated treatment in the same calendar period as the zoledronate users, and 571 new users of IV ibandronate who initiated therapy within the first 12 months after the medication was commercially available. An additional 2–7% of individuals initiated treatment but died within the 18 months after the infusion and were therefore excluded from the analysis. Use of the nonspecific HCPCS code was trivial for identifying zoledronate (1% of all infusions), but it identified ∼15% of all infusions for the IV ibandronate comparison group 2 cohort. An additional 12% of IV ibandronate infusions for both of the ibandronate cohorts were billed as outpatient (Part D) medications and taken to a health care provider rather than being billed directly by the provider as Part B medications.

Characteristics of the patients initiating IV zoledronate and ibandronate with ≥18 months of followup are shown in Table 1. Users of both IV bisphosphonates were predominantly white women. Between 23% and 40% of the individuals across the 3 cohorts had prior use of a different osteoporosis medication in the 4 months prior to the first infusion. Between approximately one-third and one-half of the infusions were first given at an outpatient infusion center rather than a physician's office. When they were given in a physician's office setting, they were more often given by a rheumatologist or an endocrinologist.

Table 1. Characteristics of individuals who were new users of IV zoledronate or ibandronate*
 Zoledronate cohort, no. (%)Comparison group 1, no. (%)Comparison group 2, no. (%)§
  • *

    A 12-month baseline period prior to the first infusion was used for covariate assessment. IV = intravenous; COPD = chronic obstructive pulmonary disease; OP = osteoporosis; n/a = not applicable given the lack of Part D pharmacy data available in the relevant time period for these individuals.

  • Zoledronate cohort: new zoledronate users during the period 9/13/07 to 9/12/08 (n = 775).

  • Comparison group 1: new ibandronate users during the period 9/13/07 to 9/12/08 (n = 275).

  • §

    Comparison group 2: new ibandronate users during the period 5/01/06 to 4/30/07 (n = 571).

Female sex761 (98.2)260 (94.5)538 (94.2)
Age at the index date, years   
 65–6964 (8.3)22 (8.0)64 (11.2)
 70–74152 (19.6)63 (22.9)129 (22.7)
 75–79246 (31.7)62 (22.5)168 (29.3)
 80–84179 (23.1)78 (28.4)126 (22.2)
 ≥85134 (17.3)50 (18.2)84 (14.6)
Geographic region   
 Northeast113 (14.6)53 (19.3)107 (18.7)
 Midwest228 (29.3)57 (20.7)150 (26.5)
 West110 (14.2)55 (20.0)97 (16.9)
 South324 (41.9)110 (40.0)217 (37.9)
Comorbidities   
 Diabetes mellitus106 (13.7)39 (14.2)55 (9.6)
 Fall-related conditions162 (20.9)53 (19.3)134 (23.5)
 COPD126 (16.3)51 (18.5)91 (15.9)
 Prior fracture79 (10.2)25 (9.1)44 (7.7)
Location/specialty of provider giving first infusion   
 Hospital-based outpatient infusion center (no provider specialty)327 (42.2)131 (47.6)176 (30.8)
 Physician office: internal medicine76 (9.8)35 (12.7)79 (13.8)
 Physician office: medical oncology112 (14.5)14 (5.1)28 (4.9)
 Physician office: rheumatology204 (26.3)73 (26.5)250 (43.8)
 Physician office: other specialty56 (7.2)22 (8.0)38 (6.6)
Prior OP drug use   
 Recent OP drug use (<4 months)308 (39.8)81 (29.5)133 (23.2)
 Remote OP drug use (4–12 months)136 (17.6)66 (24.0)n/a
 Neither331 (42.7)128 (46.5)n/a
Any oral glucocorticoid use484 (62.5)199 (72.4)264 (46.1)

At 18 months, the proportion of zoledronate users that had a PDC ≥80% was 61%. The corresponding proportion for the IV ibandronate comparison group 1 was 43%, and for comparison group 2 was 49% (P < 0.0001 for both groups compared to IV zoledronate users). Using all available data (minimum 18 months, maximum 27 months), the proportion of patients with high adherence (PDC ≥80%) for the zoledronate and the 2 ibandronate cohorts was 62.8% versus 36.0% and 33.3% (P < 0.0001 for both zoledronate/ibandronate comparisons). The distribution of the PDC (as a continuous variable) for new users of IV zoledronate and ibandronate is shown in Figure 1.

thumbnail image

Figure 1. Distribution of adherence (proportion of days covered) for new users of zoledronate and intravenous ibandronate. Proportion of days covered was measured using all data, minimum 18 months, maximum 27 months, shown as a probability density function. The y-axis represents the number of individuals at each value of proportion of the days covered.

Download figure to PowerPoint

The median and the mean of the PDC are shown in Table 2, which demonstrated that the PDC for zoledronate users was significantly greater than for each IV ibandronate cohort. For the 2 ibandronate cohorts, 18.5% and 14.0% of patients received only a single dose, which were lower than the proportion of zoledronate patients who received only a single dose (32%). If the nonspecific HCPCS codes for IV ibandronate were ignored, the mean PDC for the 2 ibandronate cohorts would have increased by 6% and 3%. Among the zoledronate cohort, 7% of the patients used a non-IV bisphosphonate osteoporosis medication at any time during followup. Within each of the 2 ibandronate cohorts, 16% and 10% used a non-IV bisphosphonate at any time during followup.

Table 2. Adherence among new users of IV bisphosphonates, using all followup time*
 Proportion of days coveredNumber of infusions
Median (IQR)Mean ± SDMedian (IQR)Mean ± SDOne only, %
  • *

    Range 18–27 months. IV = intravenous; IQR = interquartile range.

  • The proportion of days covered was compared between cohorts using nonparametric tests and was significantly greater for the IV zoledronate users compared to each IV ibandronate comparison group, P <0.0001 for each.

IV zoledronate92 (36)82 ± 182 (1)1.7 ± 0.531.9
IV ibandronate comparison group 161 (61)58 ± 314 (5)4.4 ± 2.718.5
IV ibandronate comparison group 273 (56)62 ± 315 (5)5.3 ± 2.914.0

Table 3 shows the factors associated with a low adherence to IV zoledronate. After multivariable adjustment, older patients and those with no use of osteoporosis medications in the preceding 1 year were more likely to be nonadherent. Compared to receiving the first dose of IV zoledronate in an outpatient hospital–based infusion center (and not in a physician's office), patients receiving their first dose in an internist's, rheumatologist's, or endocrinologist's office were more likely to be adherent.

Table 3. Factors associated with low adherence (<80%) to IV zoledronate*
 Crude OR (95% CI)Adjusted OR (95% CI)
  • *

    IV = intravenous; OR = odds ratio; 95% CI = 95% confidence interval.

  • Adjusted for all factors listed in this table. Dual x-ray absorptiometry (DXA) and geographic region were forced into the model based upon clinical interest. All other factors listed in Table 1 that are not represented here did not have a significant association with adherence.

Sex  
 Female1.01.0
 Male3.11 (1.03–9.37)2.30 (0.73–7.24)
Age at the index date, years  
 65–691.01.0
 70–741.01 (0.53–1.93)1.97 (0.50–1.89)
 75–791.45 (0.79–2.65)1.35 (0.73–2.51)
 80–841.57 (0.84–2.92)1.58 (0.83–2.99)
 ≥852.80 (1.47–5.31)2.87 (1.49–5.55)
Location/specialty of provider giving first infusion  
 Hospital-based outpatient infusion center1.01.0
 Internal medicine0.35 (0.19–0.63)0.35 (0.19–0.64)
 Rheumatology/endocrinology0.58 (0.40–0.84)0.59 (0.40–0.86)
 Other specialty1.21 (0.69–2.14)1.22 (0.68–2.20)
 Medical oncology0.72 (0.46–1.13)0.72 (0.45–1.15)
Prior osteoporosis drug use  
 Recent1.01.0
 Remote1.37 (0.89–2.09)1.42 (0.91–2.20)
 Neither1.73 (1.25–2.40)1.78 (1.27–2.50)
Recent DXA (within the last year)1.34 (0.99–1.81)1.34 (0.98–1.84)
Geographic region  
 Northeast1.01.0
 Midwest1.00 (0.63–1.60)0.89 (0.55–1.45)
 South0.87 (0.56–1.36)0.91 (0.57–1.44)
 West1.13 (0.66–1.93)1.12 (0.64–1.96)

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

The reasons for suboptimal patient adherence to treatment with osteoporosis medications are multifactorial. As we showed, ∼30% of zoledronate patients did not receive a second dose during a followup period that ranged between 18 and 27 months from the first dose. The mean adherence to zoledronate was 82%, which was significantly greater than the mean adherence for users of IV ibandronate (∼60%). Among the factors associated with low adherence to zoledronate were older age and receipt of the first infusion in an outpatient hospital infusion center, rather than in a physician's office.

As a practical matter, a key element of promoting adherence to an infrequent dose of IV therapy requires ensuring that the patient is scheduled to repeat the infusion and remembers to return. Verifying the reliability of the processes of care to schedule the next infusion and remind patients at the time it is needed is likely to be an important factor in ensuring high adherence to IV bisphosphonates. This is one potential explanation for why patients initiating IV bisphosphonate therapy in an outpatient infusion center were more likely to be nonadherent; specifically, it may be more difficult to coordinate processes of care to ensure that the patient continues to receive therapy and be rescheduled for the next infusion if they are receiving the infusion outside of their physician's office. Besides the use of less frequently dosed osteoporosis medications, a variety of other factors has also been suggested to improve osteoporosis medication adherence (19–22). These factors include more frequent followup, monitoring (e.g., bone turnover markers), physician education from pharmacists, and patient education and counseling via mail and telephone. Unfortunately, to date, most of these have had at best very modest effect sizes (12). Additional strategies such as those that reduce medication copayments, tailor messages to patients about their adherence, and involve the use of health information technology may hold additional promise to help improve adherence (23–25).

Although we found that adherence to IV bisphosphonate therapy was not optimal, it may be better than the adherence observed in prior reports of oral bisphosphonate users. For example, a recent systematic literature review found that 50% of oral bisphosphonate users discontinued therapy after only 6 months, and the mean medication possession ratio at 12 months was only 67% (1). For teriparatide, a parenterally administered drug given by injection once daily, only 57% of patients were persistent at 1 year (7). Adherence to zoledronate observed in this study was better than that observed in a Korean study of 259 patients, among whom only 36% returned for a second zoledronate infusion (26).

The strengths of our study include the use of national US Medicare data, which yielded results that can be generalized to the entire Medicare fee-for-service population. Also contained within the data were the setting in which the drugs were given (physician's office or hospital) and the specialty of the administering prescriber. We evaluated use of the IV bisphosphonates during the period in which they were billed using a nonspecific HCPCS code; not having used the nonspecific HCPCS codes would have misclassified ∼15% of ibandronate infusions and erroneously assigned the date of the first infusion. This would have the effect of including in the study prevalent IV bisphosphonate users (who had previously received the drug billed under a nonspecific HCPCS code) and would have misclassified them as incident users. It also would have missed incident users (who received their infusion billed via the nonspecific HCPCS code) who quickly discontinued and never went on to receive the medication billed as the specific HCPCS code. Both of these problems yielded biased estimates of adherence, resulting in better apparent adherence for IV ibandronate. The use of the nonspecific HCPCS code was less problematic for zoledronate given that it was approved for Paget's disease of bone before osteoporosis and most of its use after August 2007 was via its specific HCPCS code. Validation of the analytic procedure used to assign the nonspecific HCPCS codes is not yet available but is anticipated from ongoing work.

Our results must be interpreted in light of our study design. We required that patients have ≥18 months of observability after their index date, which excluded the small proportion of individuals who died during this followup period. This was done intentionally in order to remove individuals who might be judged not to warrant ongoing osteoporosis treatment in light of high expected near-term mortality. We also lacked information on certain covariates that might be associated with adherence such as results from bone mineral density testing; it is possible that patients with more severe osteoporosis might be more likely to persist and this might partially explain somewhat higher adherence compared with prior reports of adherence to oral bisphosphonates. We also recognize that zoledronate is approved for the prevention (as well as for the treatment) of osteoporosis, and when used for a prevention indication, it may be given every 2 years. However, Medicare does not pay for zoledronate when associated with an osteoporosis prevention diagnosis. Furthermore, zoledronate did not obtain its prevention indication until the summer of 2009, making it unlikely to have affected our results. There is no prevention indication or less frequent dosing interval available for IV ibandronate. We also lacked information on the reason for nonadherence; some nonadherence may have been deliberate on the part of patients who elected to discontinue therapy, but some may have been unintentional if both the patient and the infusion center forgot to have the patient return for retreatment (i.e., an administrative reason). Finally, we recognize that patients may have switched from IV bisphosphonates to a different non-IV osteoporosis therapy; however, this occurred in <20% of the IV bisphosphonate patients examined.

In conclusion, we found higher adherence to IV zoledronate compared to IV ibandronate and absolute rates of adherence that were lower than optimal but higher than most published studies of adherence to oral bisphosphonates. Although the results of our analysis suggest that adherence may be improved with less frequent osteoporosis medication dosing, a significant fraction of patients will still benefit from additional interventions to improve medication adherence.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Curtis had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Curtis, Yun, Matthews, Delzell.

Acquisition of data. Curtis, Yun, Matthews, Delzell.

Analysis and interpretation of data. Yun, Matthews, Saag, Delzell.

ROLE OF THE STUDY SPONSOR

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES

This research was supported by a contract between the University of Alabama at Birmingham and Amgen. Amgen had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Amgen.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. ROLE OF THE STUDY SPONSOR
  9. REFERENCES
  • 1
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