Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
Patient compliance of bisphosphonate therapy for osteoporosis appears to be suboptimal, which increases bone fracture risk.
Dentists should monitor for bisphosphonate adverse effects and if discovered, communicate the medication risk versus benefit with the physician and counsel patient not to discontinue medication unless directed by physician.
In postmenopausal women with osteoporosis, does noncompliance (compared to compliance) with bisphosphonate therapy result in more bone fractures?
The authors of this systematic review, utilizing six electronic databases, evaluated studies up to March 2009. They conducted a comprehensive search with defined inclusion and exclusion criteria. Two authors independently assessed trial quality (Newcastle-Ottawa Scale) and extracted data, with disagreements resolved through consensus. The 15 included studies were seven cohort studies, one case-control study and seven observational retrospective studies without control. The authors defined “persistence” as drug discontinuation greater than 30 days in one year, and “compliance” as the medication possession ratio (MPR), proportion of doses dispensed compared to doses prescribed.
The 15 included studies involved 704,134 post-menopausal women of which 96 percent were treated with bisphosphonates and 4 percent received hormonal therapy. Meta-analysis of five studies that followed 236,540 women for one year provided a persistence mean of 184 days. Meta-analysis of five articles that followed 234,737 women for one year had a medication possession mean of 67 percent. The authors performed three meta-analyses (Dersimonian and Laird effects model) for persistence, compliance and fracture risk. Meta-analysis of eight studies showed the probability of fracture increased 46 percent (95 percent Confidence Interval: 1.34-1.60) with non-compliance, less than 80 percent of MPR. The increased fracture probability was lower for non-vertebral (16 percent) and hip (28 percent) than for vertebral (43 percent).
The authors found persistence and compliance of bisphosphonate therapy for osteoporosis to be suboptimal. The clinical consequence is an increased risk of fracture in patients with suboptimal compliance compared to patients with good compliance.
Source of Funding:
Research and Development Programme of the Spanish Ministry of Health and Novartis Farmaceutica SA.
Importance and Context:
The most severe and costly consequences from osteoporosis are bone fractures, especially of the hip and vertebra. Randomized controlled trials have shown bone fractures to be decreased with bisphosphonate administration. The low patient compliance of prescription medications is commonly known, but the measurement of adherence to bisphosphonate therapy is not standardized within the published literature. The effectiveness of bisphosphonates could be significantly decreased by a low adherence to the prescribed therapy for osteoporosis. Research is needed to assess the incidence of bone fractures related to low patient compliance of bisphosphonate therapy.
Strengths and Weaknesses of the Systematic Review:
Two authors independently conducted a comprehensive search using defined inclusion and exclusion criteria. They assessed the quality of included studies. The authors assessed heterogeneity by a chi-square test according to the following variables: age, confirmed osteoporosis diagnosis, compliance level and drug. This study was funded in part by Novartis Pharmaceutical Corporation, a bisphosphonate manufacturer.
Strengths and Weaknesses of the Evidence:
All 15 included studies were large retrospective studies with seven studies not being controlled. There was no indication of publication bias. No randomized controlled studies were performed due to ethical concerns of withdrawing treatment. Most participants were post-menopausal women, however 2.4 percent were men. One study included women less than 45 years old. Large observational studies were not designed to follow-up persistence or compliance. Compliance was compiled from insurance databases on pharmacy refills, without verification of bisphosphonate administration. A dose-effect relationship was not verified due to a limited number of pooled studies.
Implications for Dental Practice:
It is important for dentists to understand the benefits of bisphosphonate therapy in decreasing the subsequent high morbidity from bone fractures before discussing possible low-morbidity dental risks associated with bisphosphonates. Dentists should monitor for bisphosphonate adverse effects and if discovered, communicate the medication risk versus benefit with the physician and patient. Patients should be counseled to continue bisphosphonate therapy until discontinued by their physician. The ADA Council on Scientific Affairs issued a November 2011 report on Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis. (1)