Fear of falling, fracture history, and comorbidities are associated with health-related quality of life among European and US women with osteoporosis in a large international study.

UNLABELLED: We studied 7,897 women with postmenopausal osteoporosis to assess factors that influence health-related quality of life (HRQoL). An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL. Understanding the factors that affect HRQoL may improve management of these patients. INTRODUCTION: HRQoL is impaired in women treated for postmenopausal osteoporosis (PMO). The objective of this study was to examine the relationship between clinical characteristics, comorbidities, medical history, patient demographics, and HRQoL in women with PMO. METHODS: Baseline data were obtained and combined from two large and similar multinational observational studies: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) and in the US (POSSIBLE US™) including postmenopausal women in primary care settings initiating or switching bone loss treatment, or who had been on bone loss treatment for some time. HRQoL measured by health utility scores (EQ-5D™) were available for 7,897 women (94 % of study participants). The relationship between HRQoL and baseline clinical characteristics, medical history and patient demographics was assessed using parsimonious, multivariable, mixed-model analyses. RESULTS: Median health utility score was 0.80 (interquartile range 0.69-1.00). In multivariable analyses, young age, low body mass index, previous vertebral fracture, increased number of comorbidities, high fear of falling, and depression were associated with reduced HRQoL. Regression-based model estimates showed that previous vertebral fracture was associated with lower health utility scores by 0.08 (10.3 %) and demonstrated the impact of multiple comorbidities and of fear of falling on HRQoL. CONCLUSIONS: In this large observational study of women with PMO, there was substantial interindividual variability in HRQoL. An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL.

Adherence with bisphosphonate therapy and change in bone mineral density among women with osteoporosis or osteopenia in clinical practice.

UNLABELLED: In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management. INTRODUCTION: In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy-overall and by level of adherence-is largely unknown. METHODS: A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score<-1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan. RESULTS: Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm2, and pretreatment T-score was -1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95% CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5% (1.1 and 1.9%). Within the MPR strata (five consecutive equi-intervals, from low (0-0.19) to high (0.80-1.0)), mean change in BMD was -0.8% (-1.6 and 0.1%), 0.7% (-0.3 and 1.7%), 2.1% (1.1 and 3.0%), 2.1% (1.4 and 2.9%), and 2.9% (2.3 and 3.5%), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4-3.4%, p<0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0-0.19. CONCLUSIONS: Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD.

Treatment satisfaction and persistence among postmenopausal women on osteoporosis medications: 12-month results from POSSIBLE US™.

SUMMARY: Women in POSSIBLE US™ who expressed greater treatment satisfaction at study entry were more likely to persist with osteoporosis therapy over a 1-year period. Lower satisfaction among women with moderate/severe side effects increased the risk of discontinuation/switching by 67%. Treatment satisfaction and side effect experience influence osteoporosis medication adherence. INTRODUCTION: Non-adherence is common among women using postmenopausal osteoporosis (PMO) medications. We describe the association between treatment satisfaction, measured with the Treatment Satisfaction Questionnaire for Medication (TSQM), and the risk of discontinuation/switching PMO medications using patient-reported data from a large, longitudinal cohort study. METHODS: Data from 2,405 participants in the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™) Study were evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HR) for the association between treatment satisfaction at study entry and self-reported discontinuation/switching of pharmacologic PMO medications over a 1-year follow-up period. Logistic regression was used to evaluate relationships between treatment satisfaction, lifestyle behaviors, and compliance with bisphosphonate dosing instructions. RESULTS: Median TSQM scores were highest (indicating greatest satisfaction) for the side effects domain [n = 1,182; median = 87.5 (Q1 = 75.0, Q3 = 100.0)] and lowest for global satisfaction [n = 2,340; median = 64.0 (Q1 = 55.7, Q3 = 77.7)]. Median scores decreased for the side effects and global satisfaction domains as patient-reported side effect severity increased. Women with higher satisfaction were less likely to discontinue/switch medications than women with lower scores (adjusted HRs for convenience 0.73, 95% CI = 0.63-0.85; effectiveness 0.82, 95% CI = 0.70-0.97; and global satisfaction 0.73, 95% CI = 0.63-0.85). Lower treatment satisfaction was particularly influential among women who reported moderate/severe side effects (HR = 0.60, 95% CI = 0.37-0.97). CONCLUSIONS: Lower treatment satisfaction was associated with a 22% (1/0.82) to 67% (1/0.60) increased risk of discontinuation/switching osteoporosis medication during 1 year of follow-up.

Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women.

UNLABELLED: The final analysis of this 2-year, randomized, crossover study showed that postmenopausal women with osteoporosis were more adherent, compliant, and persistent with subcutaneous denosumab injections every 6 months than with once-weekly alendronate tablets. After receiving both treatments, women reported greater satisfaction with injectable denosumab and preferred it over oral alendronate. INTRODUCTION: Osteoporosis patients who are non-compliant or non-persistent with therapy may have suboptimal clinical outcomes. This 2-year, randomized, open-label, crossover study compared treatment adherence between subcutaneous denosumab, 60 mg every 6 months, and oral alendronate, 70 mg once weekly. METHODS: Postmenopausal women at 25 centers in the USA and Canada with bone mineral density T-scores -4.0 to -2.0 and no prior bisphosphonate use received alendronate then denosumab, or denosumab then alendronate, over successive 12-month periods. Adherence required both compliance (denosumab injections 6 months apart or ≥ 80% of alendronate tablets) and persistence (both denosumab injections or ≥ 2 alendronate doses in the last month and completion of the treatment period). RESULTS: Of the 250 women enrolled (124 alendronate, 126 denosumab), 221 entered the second year (106 denosumab, 115 alendronate). Denosumab was associated with less non-adherence than alendronate (first year, 11.9% vs 23.4%; second year, 7.5% vs 36.5%). Risk ratios for non-adherence, non-compliance, and non-persistence favored denosumab in both years (p < 0.05). Of 198 subjects expressing treatment preference, 183 (92.4%) preferred the injections over the oral therapy. BMD improved further when subjects received denosumab after alendronate and remained stable when they received alendronate after denosumab. CONCLUSION: Based on the final results of this crossover study after women had received each treatment for up to 1 year, postmenopausal women with osteoporosis were more adherent, compliant, and persistent with subcutaneous denosumab injections every 6 months than with once-weekly alendronate tablets and reported increased treatment preference and satisfaction with injectable denosumab over oral alendronate.

Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial.

UNLABELLED: In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain. INTRODUCTION: In the FREEDOM trial, denosumab significantly reduced the risk of new vertebral, hip, and nonvertebral fractures. We evaluated the effect of denosumab on HRQoL and the association between incident clinical fractures and HRQoL. METHODS: The FREEDOM trial enrolled 7,868 women aged 60-90 years with a total hip and/or lumbar spine BMD T-score <-2.5 and not <-4.0 at either site. Women were randomized to receive denosumab 60 mg or placebo every 6 months, in addition to daily calcium and vitamin D. HRQoL was assessed with the Osteoporosis Assessment Questionnaire-Short Version (OPAQ-SV) at baseline and every 6 months for 36 months. The OPAQ-SV assesses physical function, emotional status, and back pain. Higher scores indicate better health status. RESULTS: No statistically significant differences in mean change in HRQoL from baseline to end of study were found when comparing treatment groups. Compared with women without any incident fractures during the study, women with incident clinical fractures reported significant declines in physical function (-4.0 vs. -0.5) and emotional status (-5.0 vs. -0.8) at month 36 (P < 0.001 for both). Importantly, time-dependent covariate analyses demonstrated that the largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain. CONCLUSIONS: These findings not only demonstrate that incident clinical fractures impact HRQoL but also contribute new information regarding the impact of these fracture events on HRQoL over time.

Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate.

UNLABELLED: In this study, 250 women with osteoporosis were randomized to 12 months with subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg once weekly, then crossed over to the other treatment. The primary endpoint, treatment adherence at 12 months, was 76.6% for alendronate and 87.3% for denosumab. INTRODUCTION: The purpose of this study is to evaluate treatment adherence with subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg once weekly. METHODS: In this multicenter, randomized, open-label, 2-year, crossover study, 250 postmenopausal women with low bone mineral density received denosumab or alendronate for 12 months, then the other treatment for 12 months. The alendronate bottle had a medication event monitoring system cap to monitor administration dates. Definitions were as follows: compliance, receiving both denosumab doses 6 (± 1) months apart or 80-100% of alendronate doses; persistence, receiving both denosumab doses and completing the month 12 visit within the visit window or ≥ 2 alendronate doses in the final month; adherence, achieving both compliance and persistence. This report includes data from the first 12 months. RESULTS: The primary study endpoint, adherence in the first 12 months, was 76.6% (95/124) for alendronate and 87.3% (110/126) for denosumab. Risk ratios for denosumab compared with alendronate at 12 months were 0.58 (p = 0.043) for non-adherence, 0.48 (p = 0.014) for non-compliance, and 0.54 (p = 0.049) for non-persistence. Subject ratings for treatment necessity, preference, and satisfaction were significantly greater for denosumab and ratings for treatment bother were significantly greater for alendronate. Adverse events were reported by 64.1% of alendronate-treated subjects and 72.0% of denosumab-treated subjects (p = 0.403). The most common adverse events were arthralgia, back pain, pain in extremity, cough, and headache (each in <10% of subjects in each group). CONCLUSIONS: Significantly greater treatment adherence was observed for subcutaneous administration of denosumab every 6 months than for oral alendronate once weekly.

Cost of fractures commonly associated with osteoporosis in a managed-care population.

OBJECTIVE: To examine direct costs of hip, vertebral, and non-hip non-vertebral (NHNV) fractures, and to estimate the rate of osteoporosis (OA) diagnosis and treatment in the fracture population. METHODS: Subjects ≥ 45 years with a new hip, vertebral, or NHNV fragility (closed) fracture between June 30, 2002 and June 30, 2006 were studied retrospectively. All-cause and fracture-specific medical costs were calculated from medical claims in the 12-month baseline and follow-up periods. Total healthcare costs included pharmacy and medical costs. Diagnosis for OA and OA treatment were identified in both the baseline and follow-up period from diagnosis codes on medical claims for OA, and from pharmacy claims for treatment. Analyses were performed separately for commercial (COM) and Medicare Advantage (MA) populations and stratified by fracture type. Generalized linear models were estimated for total follow-up healthcare cost. RESULTS: The study sample included 36,521 COM and 10,160 MA subjects. Hip fracture subjects had the highest follow-up medical costs in unadjusted and adjusted analyses (COM: mean $35,898; median $22,945; MA: mean $32,919; median $26,047). Follow-up costs were much higher than baseline costs. Fracture-related costs accounted for a large proportion of follow-up medical costs. Although rates of osteoporosis diagnosis and treatment increased from baseline to follow-up, the majority of both COM and MA subjects had no evidence of osteoporosis diagnosis or treatment in either period. CONCLUSIONS: Despite limitations of this study, including conventional generalizability issues, and sensitivity and specificity of claims-based diagnoses, results are consistent with other research and provide compelling results of substantial cost burden of fractures related to osteoporosis. Low rates of osteoporosis diagnosis and treatment among patients with costly fragility fractures underscore the opportunity for managed care organizations to initiate comprehensive disease management programs in osteoporosis.

Physician perception of patient adherence compared to patient adherence of osteoporosis medications from pharmacy claims.

OBJECTIVE: This study explored physicians' perceptions of patient adherence to medications compared with patient adherence derived by administrative data in the treatment of osteoporosis. RESEARCH DESIGN AND METHODS: A study involving written questionnaires from prescribers treating patients with postmenopausal osteoporosis (PMO) compared the questionnaire responses to pharmacy claims of these prescribers' patients' refill patterns. Approximately 2000 physicians from a large US health plan were faxed or mailed a survey. Data from the physician survey were merged with administrative claims data of the participating physicians' patients. RESULTS: A total of 412 physicians (21.8%) responded. Although a low response rate, there were no significant demographic differences between participating and non-participating physicians. Surveyed physicians reported that 66% of their patients had private/commercial coverage and over 60% reported seeing their PMO patients annually. Overall, physicians estimated that 69.2% of patients were adherent 80% of the time after 12 months of therapy. Yet, pharmacy claims data for those physicians' patients indicated 48.7% of patients were adherent (defined as having an MPR of >or=80%) after 12 months of therapy. Physicians overestimated their patients' adherence regardless of medication class and across physician specialties. Regression modeling revealed that physicians who have been in practice longer estimated fewer patients as adherent, whereas those who prescribe more PMO treatments estimate a greater number of patients as adherent. Providers cited side effects and affordability of medication as the most frequent reasons for non-adherence. CONCLUSIONS: Physicians overestimate patient adherence to PMO therapies. Improving physician awareness of medication non-adherence to PMO therapies may facilitate physician-patient dialogue, with the aim of identifying patient-centered reasons for non-adherence. These discussions are important because patients with poorer adherence have a higher risk of fracture. Future research should focus on reasons for patient non-adherence to osteoporosis regimens and intervention strategies that improve communication between the provider and patient. Findings must be considered within the limitations of this claims database analysis. Some degree of incomplete or incorrect coding may exist, and the presence of a claim for a filled prescription does not indicate that the medication was consumed or taken as prescribed. Patients included in the study are not necessarily representative of all patients being treated for osteoporosis.

Preference and satisfaction with a 6-month subcutaneous injection versus a weekly tablet for treatment of low bone mass.

UNLABELLED: The Preference and Satisfaction Questionnaire (PSQ) compares patient preference and satisfaction between a 6-month subcutaneous injection and weekly oral tablet for treatment of bone loss. Patients preferred and were more satisfied with a treatment that was administered less frequently, suggesting the acceptability of the 6-month injection for treatment of bone loss. INTRODUCTION: The PSQ compares patient preference and satisfaction between a 6-month subcutaneous injection and a weekly oral tablet for treatment of bone loss. METHODS: Postmenopausal women with low bone mass who enrolled in two separate randomized phase 3 double-blind, double-dummy studies received a 6-month subcutaneous denosumab injection (60 mg) plus a weekly oral placebo or a weekly alendronate tablet (70 mg) plus a 6-month subcutaneous placebo injection. After 12 months, patients completed the PSQ to rate their preference, satisfaction, and degree of bother with each regimen. RESULTS: Most enrolled patients (1,583 out of 1,693; 93.5%) answered >or=1 item of the PSQ. Significantly more patients preferred and were more satisfied with the 6-month injection versus the weekly tablet (P < 0.001). More patients reported no bother with the 6-month injection (90%) than the weekly tablet (62%). CONCLUSION: Patients preferred, were more satisfied, and less bothered with a 6-month injection regimen for osteoporosis.

Compliance with osteoporosis drug therapy and risk of fracture.

INTRODUCTION: Patient compliance with osteoporosis drug therapy is often poor in clinical practice and may be associated with higher risk of fracture. METHODS: A nested case-control study was undertaken using a US health insurance claims database. The source population included all women aged >or=45 years who began drug therapy for osteoporosis. Cases consisted of those who experienced an osteoporosis-related fracture; they were matched to controls without osteoporosis-related fracture. Compliance with osteoporosis drug treatment was assessed in terms of the number of therapy-days received and medication possession ratio (MPR). Conditional logistic regression was employed to examine the relationship between compliance and fracture risk. RESULTS: A total of 453 women with osteoporosis-related fracture were identified and matched to 2,160 controls. Fracture risk was significantly lower for patients with >180 days of therapy [181-360 days: odds ratio (OR) = 0.70, 95% CI = 0.49-0.99; >360 days: OR = 0.65, 95% CI = 0.43-0.99) versus those with or=90% (OR = 0.70, 95% CI = 0.52-0.93) versus those with MPR <30%. Fracture risk decreased as compliance increased (p(trend) < 0.05). CONCLUSION: Among women initiating drug therapy for osteoporosis, better compliance is associated with reduced risk of fracture.

Compliance with drug therapy for postmenopausal osteoporosis.

INTRODUCTION: Patient compliance with pharmacotherapy for osteoporosis is typically poor in clinical practice; less frequent dosing with bisphosphonates may improve compliance. METHODS: Using data from 49 US health plans, we identified all women aged >/=45 years with osteoporosis who initiated therapy with a bisphosphonate, calcitonin, estrogen, or raloxifene. Compliance was examined alternatively in terms of incidence of adherence failure (medication days <80% of possible) and persistence failure (gap in therapy >/=90 days), and was compared across treatment groups using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: The study population included 18,822 women, 48% of whom initiated weekly bisphosphonate therapy. Overall risk of adherence failure was 47% at 3 months, 70% at 1 year, and 84% at 3 years. Risk of persistence failure was 47% at 1 year, and 77% at 3 years. In multivariate analyses, risk of adherence failure was higher for calcitonin (hazard ratio=2.7 vs weekly bisphosphonate therapy, p<0.01), but comparable for all other therapies. Relative risks of persistence failure were generally similar. CONCLUSIONS: Approximately three-quarters of women who initiate osteoporosis drug therapy are non-adherent with treatment within 12 months, and almost 50% have discontinued such therapy by this time. Compliance with weekly bisphosphonate therapy is generally no better than that with osteoporosis medications requiring more frequent dosing.