Loss of treatment benefit due to low compliance with bisphosphonate therapy.
Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR >or=80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit.


BACKGROUND
Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit.


METHODS
New female users of alendronate or risedronate between 1999-2004, aged >or=45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of >or= 2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression.


RESULTS
The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR >or= 80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR >or= 90%.


CONCLUSIONS
These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit.
Penning-van Beest
F J A
FJ
PHARMO Institute, P.O.Box 85222, 3508, AE Utrecht, The Netherlands. fernie.penning@pharmo.nl
Erkens
J A
JA
Olson
M
M
Herings
R M C
RM
D000368:Aged; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D009426:Netherlands; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D018570:Risk Assessment / Q000706:statistics & numerical data; D016896:Treatment Outcome; D016312:Treatment Refusal / Q000523:psychology / Q000706:statistics & numerical data*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates