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Table 1 Bisphosphonates adherence for treatment of osteoporosis: studies and main findings

From: Bisphosphonates adherence for treatment of osteoporosis

Author (Year) Study design Sample Main findings
Barret-Connor et al. [5] Cohort study 2,405 women on osteoporosis medications- 76% taking BP Lower treatment satisfaction was associated with 22% to 67% increased risk of discontinuation/switching osteoporosis medication during 1styear of follow-up
Ström, et al. [9] Cohort study 36,433 participants taking risedronate or alendronate Automatic generic substitution may have reduced persistence in participants taking alendronate. No difference was observed in persistence with proprietary risedronate during the same period.
Roux et al. [27] Randomized controlled trial 212 women with post menopausal osteoporosis (interventions group) and 285 women with osteoporosis post menopausal in control group- multicenter study in France This study failed to demonstrate that monitoring a serum bone turnover marker impact the persistence with monthly ibandronate treatment.
Palacios et al. [20] Observational, prospective, multicenter trial 174 women taking weekly alendronate Treatment with Alendronate in women with postmenopausal osteoporosis reduces the urinary excretion of the bone turnover biomarker N-telopeptide (NTx). The probability of achieving a clinically significant reduction is greater in those women with higher baseline levels of NTx and in women who comply with treatment.
Lai et al. [22] Cross-sectional observational study 1,130 survivors of minimal trauma hip fracture admitted to a hip fracture unit (19.2% rural patients). Following fracture, only 623 patients (55.1%) were available. Before fracture, fewer rural patients had taken BPs (7.7% versus 13.3%). Following fracture, more rural then urban patients were significantly non-compliant with BPs (44% versus 52.4%). The compliance among both rural and urban patients decreased, following hip fracture.
Bryl et al. [2] Randomized controlled trial 42 physicians from 5 medical centers and 656 patients (Therapeutic program: Alendronate 70 mg) 56% of patients regarded the therapy as convenient. Patients more often accepted their disease and treatment if their physicians obtained high scores in the Social Competence Questionnaire. When physician competence regarding close emotional contact was high, only 15% of the patients revealed symptoms of fear of disease and treatment, in comparison to 40% of the patients, if the competence of the physician was low.
Curtis et al. [23] Cohort study 775 taking zoledronate; 275 taking ibandronate (comparison group 1); 571 taking ibandronate (the first year that ibandronate was available- comparison group 2). Using all available data (minimum 18 months, maximum 27 months), the proportion of patients with high adherence for the zoledronate and the 2 ibandronate cohorts was 62.8% versus 36.0% and 33.3%. But approximately 30% of patients taking zoledronate did not receive a second infusion.
Devold et al. [18] Cohort study 7,610 patients, all incident taking alendronate. In women, the most important factors for being adherent were advanced age and high income. In men, a middle educational level predicted adherence.
Devine et al. [10] Cohort study 22,363 new users of an oral BP(alendronate, risedronate, or ibandronate). Weekly cohort, n = 15,228; Monthly cohort, n = 7,225. Patients receiving oral BPs on a monthly basis showed higher rates of medication compliance compared to weekly dosage in our study. However, compliance with BPs among all new patients was suboptimal (compliance- 43%)
Burden et al. [11] Cohort study 451,113 new BP patients: alendronate (5, 10, and 70 mg), cyclical etidronate and risedronate (5 /35 mg) Persistence with therapy declined from 63% at 1 year to 46% at 2 years and 12% at 9 years. Most patients experienced one or more extended gaps in BP therapy.
Hadji et al. [13] Cohort study 4,147 women treated with oral BP Persistence rates after 1 and 2 years were 27.9% and 12.9%, respectively, and 66.3% of women were compliant. After 24 months of therapy, compliant women had fewer fractures than non-compliant women. Compliance and persistence were inadequate.
Kuzmanovaet al. [1] Randomized Controlled Trial 341 postmenopausal women taking -weekly alendronate or mensal ibandronate There was a very good patient medication adherence of the study subjects to the 24-month treatment with BPs. MPR ranged from 0,93 to 1,0. The patient medication persistence dropped significantly at the end of month 12.
Lai et al. [24] Randomized controlled trial 198 patients( weekly alendronate or risedronate) : intervention = 100 (received a ‘counselling package’); control = 98 (no counselling). When adherence was assessed by pill count, the intervention group showed a significantly higher adherence. Overall, persistence at 1 year was high and similar between groups.
Montori et al. [25] Randomized controlled trial 100 patients: the control group received the National Osteoporosis Foundation booklet, “Boning Up On Osteoporosis: A Guide To Prevention and Treatment.” Most patients exhibited optimal medication adherence and persistence at 6 months. Analyses of adherence or persistence did not show any significant effect of the decision aid on 6-month adherence BPs.
Ojeda- Bruno et al. [15] Cohort study 683 patients older than 50 years with a fragility fracture were appointed for a clinical visit Attendance of scheduled visits was associated with adherence to BPs.
Cheen et al.[12] Retrospective observational study 798 patients with osteoporosis- oral BP users The study suggests high adherence rates to BP therapy amongst Singaporean patients (mean MPR was 78,9% +/− 27,5% and 69% of the patients were persistent with therapy at 1 year).
Cottéet al. [6] Retrospective observational study 2,990 women taking-weekly(alendronate or risedronate) or monthly ibandronate. Adherence to a monthly BP treatment regimen is higher than that to weekly regimens. Patients treated with a monthly regimen were 37% less likely to be non-persistent and were more compliant, with a 5% higher absolute MPR, than women treated with weekly regimens.
Curtis et al. [26] Randomized controlled study 3,169 women with low bone mass taking placebo The study found small but significant differences in the change in hip bone mineral density between women with high compliance versus low compliance with placebo.
Briesacher et al. [14] Cohort study 1,835 individuals who switched to once-monthly BPs The once-monthly switch was associated with less adherence failure (4% fewer patients per month pre-switch vs. 1% fewer patients per month post-switch; but the impact on fracture risk was uncertain.
Muratore et al. [3] Randomized controlled trial 60 women with postmenopausal osteoporosis – randomized to two groups: group A: Clodronate (CLD) every month for 12 months, and group B: CLD every 2 weeks for 12 months A significant increase of BMD in both groups and in both skeletal sites was observed at 12 months versus baseline. No difference was observed between groups. The “twice-a-month” regimen with 200 mg IM CLD may well promote an improved adherence with the same clinical efficacy and safety profile.
Patrick et al. [4] Cohort study 19,987 patients >65 years old taking BP The fractures occurred at a rate of 43 to 1,000 people/year, showing an inverse relationship between drug adherence and fracture rate for all measures of adherence and fracture types, excluding distal forearm fractures
Dugard et al. [16] Cohort study 254 women with osteoporosis 38% patients failed to start treatment, associated with higher BMD Z score and residence in a nursing/residential home. Persistence was associated with a lower comorbidity index and compliance with a lower BMD Z score and fall before starting treatment.
Curtis et al. [7] Retrospective observational study 101,038 new patients taking BP; 38205 on one or more concomitant therapies At 1 year, the proportion of persons with high BP compliance (MPR 80%) was 44%. The statin MPR variable was the most significant predictor of 1-year BP compliance, followed by age and prior receipt of BMD testing.
Sheehy et al. [17] Cohort study 32,804 patients with osteoporosis taking BP oral (weekly alendronate or risedronate) In the primary prevention cohort, the risk of osteoporotic fractures in the year following BP therapy initiation was reduced by 49% for compliant versus non-compliant patients. In the secondary prevention cohort, the risk of subsequent osteoporotic fracture was reduced by 57% for compliant patients versus non-compliant patients.
Sheehy et al. [8] Cohort study 32,804 patients taking weekly risedronate or weekly alendronate(brand or generic) Patients initiated on weekly oral generic alendronate showed a statistically significant lower persistence to BP therapy compared to patients initiated on weekly oral branded risedronate and weekly oral branded alendronate.
Berecki-Gisolf et al. [19] Cohort study 788 elderly women after osteoporotic fracture- BP users Adherence to BP treatment by older Australian women with estabilished osteoporosis was poor; within 6 months of starting, half the women stopped their treatment. Adherence failure was more likely among smokers and women taking acid-related medication and less likely among women reporting high levels of physical activity.
Ideguchi et al. [21] Cohort study 146 patients with osteoporosis - BP users that switched for a second drug Patients who switched BPs had high rates of persistence of therapy. Those who stopped their first BP because of adverse effects were at risk of discontinuing the second drug for the same reason.