Friday, May 3, 2013

Bisphosphonates associated with improved hip, knee implant survival

[Bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis.[1] They are called bisphosphonates because they have two phosphonate (PO3) groups and are similar in structure to pyrophosphate.
Evidence shows that they reduce the risk of osteoporotic fracture in those who have had previous fractures]

Clinical Endocrinology News


The rate for revision surgery at a median of 2.6 years’ follow-up was 1.88% in the 1,911 participants who had taken bisphosphonates for at least 6 months, compared with 4.36% in the 10,755 nonbisphosphonate users (hazard ratio, 0.62).
"The observed effect size is stronger in patients with higher therapy duration and adherence," Dr. Daniel Prieto-Alhambra reported at the annual meeting of the British Society for Rheumatology.
"This association does not differ by age, gender, joint replaced, or fracture history," added Dr. Prieto-Alhambra, senior clinical research fellow from the Nuffield department of orthopaedics, rheumatology, and musculoskeletal sciences at the University of Oxford, England.
Osteolysis and aseptic loosening are the most common causes of revision surgery, the researcher noted, adding that bisphosphonates have antiosteoclast activity that may have potential benefits on implant survival.
"Patients need to be on treatment for at least 6 months for the drug to be effective," Dr. Prieto-Alhambra emphasized. He later said after his presentation that data from a sub-analysis suggest that patients benefit further if they started therapy in the weeks following surgery.*
Data used in the study were obtained from Danish nationwide health registries on more than 80,000 patients aged 40 years or older who had total hip arthroplasty (THA) or total knee arthroplasty (TKA) in Denmark between 1998 and 2007. Patients were excluded if they had experienced a prior hip fracture; had inflammatory arthritis or used disease-modifying antirheumatic drugs; or had Paget’s disease, bone cancer, or metastasis. Baseline characteristics of those who did and those who did not use bisphosphonates were comparable except for calcium and vitamin D supplementation, which was higher in the bisphosphonate-treated group (9.9% vs. 4.8%).
The longer the duration of treatment, the less chance there was for implant failure: 5 implants failed in 352 (1.4%) patients treated with bisphosphonates for more than 2 years (HR, 0.53); 16 (1.6%) in 1,006 patients treated for 1-2 years (HR, 0.52); and 15 (2.7%) in 553 patients treated for 6-12 months (HR, 1.31).
Adherence was assessed using a medication possession ratio (MPR), with lower MPR values indicating poorer adherence. Failure rates were 3%, 2.9%, and 1.5% for MPRs of less than 0.5 (HR, 0.93), 0.5-0.79 (HR, 0.48), and 0.8 or greater (HR, 0.56), respectively.
The study’s findings support those of a recent U.K. population-based, retrospective cohort study (BMJ 2011 [doi:10.1136/bmj.d7222]) that involved more than 41,000 primary THA/TKA patients.
The U.K. data showed that fewer surgical revisions occurred at 5 years in bisphosphonate users (0.93% vs. 1.96% in nonusers), and that there was a 46% decrease in the risk of revision surgery (HR for implant survival of 0.54; P = .047). It was also estimated, however, that at least 107 patients would need to be treated with bisphosphonates to avoid one revision surgery.
Osteoarthritis accounts for more than 90% of THAs and TKAs performed in the United Kingdom, with 1 in 75 patients experiencing implant failure and revision surgery within 3 years of the index surgery. Such surgery is associated with a worse clinical outcome than the primary procedure, and it is also associated with greater health care costs (PLoS Med. 2008;5:e179). Bisphosphonates could potentially offer a simple and hopefully cost-effective solution to reducing the likelihood of such surgery.
irmation in a randomized controlled trial is needed to test the efficacy of bisphosphonates to improve implant survival, Dr. Prieto-Alhambra said.
A 40% reduction in the risk of aseptic loosening of the prosthesis is potentially very good news for patients, observed Dr. Ken Poole, a clinical lecturer at the University of Cambridge, England. Randomized trial data would be welcomed and warranted, he added.
Dr. Poole, who was chairing the session at which these data were presented, highlighted that this was another "good news" story for bisphosphonates, adding to recent evidence that they increased survival after hip fracture and have also been associated with reductions in the incidence of certain cancers.
"Many of my patients are well versed in the potential harms of bisphosphonate treatments for osteoporosis, often because of enthusiastic media coverage of the ‘bad news’ aspect," he said in an interview.
"The upshot is that ‘at-risk’ patients are increasingly reluctant to commence therapy; indeed, it is easy to find out about rare and frightening side effects like osteonecrosis of the jaw and atraumatic fractures of the femur from a few clicks on the Internet," Dr. Poole commented.
Although serious adverse events should be borne in mind when considering treatment choice, Dr. Poole noted that bisphosphonates were effective for osteoporosis in the right patients, and that Dr. Prieto-Alhambra’s study was one of several identifying additional health benefits in patients undergoing total hip or knee replacement.
A poor public perception of bisphosphonates could influence adherence, and there is recent evidence that only 30% of women actually take their prescriptions to the pharmacist (Osteoporos. Int. 2013 [doi:10.1007/s00198-013-2326-5]). Concern over calcium supplementation causing heart attacks and stroke might also be a factor, as this, together with vitamin D, goes along with bisphosphonate use. Indeed, a study of 233 women taking bisphosphonates for osteoporosis also presented at the British Society for Rheumatology meeting found that a lack of concomitant calcium and vitamin D supplementation was predictive of poor adherence (Rheumatology 2013;52[Suppl. 1]:i116-7; abstract 163). Other predictive factors were older age and the use of sleeping tablets.
Dr. Prieto-Alhambra and Dr. Poole had no conflicts of interests.
* Revised, 5/1/13

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