Medical Studies

For Immediate Release: October 13, 2010 Media Inquiries: Karen Riley, 301-796-4674, karen.riley@fda.hhs.gov Consumer Inquiries: 888-INFO-FDA

   FDA: Possible increased risk of thigh bone fracture with bisphosphonates Labeling change adds warning about possible risks of long-term use of osteoporosis drugs  

The U.S. Food and Drug Administration today warned patients and health care providers about the possible risk of atypical thigh bone (femoral) fracture in patients who take bisphosphonates, a class of drugs used to prevent and treat osteoporosis. A labeling change and Medication Guide will reflect this risk.

Bisphosphonates inhibit the loss of bone mass in people with osteoporosis. Bisphosphonates have been shown to reduce the rate of osteoporotic fractures -- fractures that can result in pain, hospitalization, and surgery-- in people with osteoporosis. While it is not clear whether bisphosphonates are the cause, atypical femur fractures, a rare but serious type of thigh bone fracture, have been predominantly reported in patients taking bisphosphonates. The optimal duration of bisphosphonate use for osteoporosis is unknown, and the FDA is highlighting this uncertainty because these fractures may be related to use of bisphosphonates for longer than five years.

The labeling changes and Medication Guide will affect only those bisphosphonates approved for osteoporosis, including oral bisphosphonates such as Fosamax, Fosamax Plus D, Actonel, Actonel with Calcium, Boniva, Atelvia, and their generic products, as well as injectable bisphosphonates such as Reclast and Boniva.

Labeling changes and the Medication Guide will not apply to bisphosphonates used for Paget's disease or cancer/hypercalcemia such as Didronel, Zometa, Skelid, and their generic products.

"The FDA is continuing to evaluate data about the safety and effectiveness of bisphosphonates when used long-term for osteoporosis treatment," said RADM Sandra Kweder, M.D., deputy director, Office of New Drugs in the FDA's Center for Drug Evaluation and Research. "In the interim, it's important for patients and health care professionals to have all the safety information available when determining the best course of treatment for osteoporosis."

Today's warning follows a March 10, 2010, Drug Safety Communication announcing the FDA's ongoing safety review of bisphosphonate use and the occurrence of atypical femur fractures. The FDA has since reviewed all available data on bisphosphonate use, including data summarized in the American Society for Bone Mineral Research Task Force report. The report recommended additional product labeling, better identification and tracking of patients experiencing these breaks, and more research to determine whether and how these drugs cause the serious but uncommon fractures.

Based on the FDA's review, the Warnings and Precautions section of all bisphosphonate products for osteoporosis will be revised, and the FDA will require the inclusion of a Medication Guide to better inform patients of the possible increased fracture risk.

The FDA recommends that health care professionals be aware of the possible risk in patients taking bisphosphonates and consider periodic reevaluation of the need for continued bisphosphonate therapy for patients who have been on bisphosphonates for longer than five years.

Patients taking bisphosphonates for osteoporosis should not stop using their medication unless told to do so by their health care professional. Those taking bisphosphonates also should report any new thigh or groin pain to their health care provider and be evaluated for a possible femur fracture. Patients and health care professionals should report side effects with the use of bisphosphonates to the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch or by calling (800) 332-1088.

For more information: FDA Drug Safety Communication Consumer Update: Possible Fracture Risk With Osteoporosis Drugs

U.S. FDA to Collect Adverse Event Data Despite UK Recall of Metal Hip Implants

Quality problems with metal-on-metal (MoM) hip replacement systems, like Johnson & Johnson (J&J)’s ASR devices, may not be as widespread as UK data indicates, the U.S. Food and Drug Administration (FDA) says. National Joint Registry of England and Wales data, which last year showed high revision rates for two ASR hip resurfacing systems, led to a UK medical device alert and recommended blood tests, as well as a worldwide J&J recall in August. But the FDA argues the adverse event rate for these devices remains unclear, and the agency is in the process of gathering additional information about adverse events in people with MoM hip implants.

Read More Here http://fdanews.com/newsletter/article?issueId=14568&articleId=135224

Staples significantly increase risk of postoperative infection study

March 2010 Original Link  http://www.orthosupersite.com/view.aspx?rid=62584

The use of staples to close wounds following orthopedic surgery - especially hip surgery - is associated with a significantly greater risk of wound infection than traditional suturing, according to orthopedic researchers from Norwich, England.

Six clinical trials

Toby O. Smith, MSc, BSc (Hons), MCSP, and colleagues analyzed the results of six trials that compared staples and sutures used for wound closure following orthopedic procedures in adult patients. The six clinical trials involved 683 wounds. Of these cases, 322 patients underwent suture closure and 351 patients had staple closure, according to a British Medical Journal press release.

The authors found that wounds closed with staples were more than three times as likely to develop a superficial wound infection compared to wounds closed with sutures. In a subgroup analysis of patients undergoing hip surgery, the risk of developing a wound infection was found to be four times greater after staple closure than suture closure, according to the release.

Staples not recommended

The researchers found no significant difference between staples and sutures in the development of inflammation, discharge, dehiscence, necrosis and allergic reaction.

The authors called for high quality, well-designed trials to confirm their findings.

Although the quality of evidence from the six trials was generally poor, the authors concluded, "With the current evidence, however, patients and doctors should think more carefully about the use of staples for wound closure after hip and knee surgery."

•Reference:
Smith TO, Sexton D, Mann C, et al. Sutures versus staples for skin closure in orthopaedic surgery: meta-analysis. BMJ. [Published online ahead of print March 16, 2010]

A Modified Posterior Approach Preserves Femoral Head Oxgenation During Hip Resurfacing 2010

Steffen RT, De Smet KA, Murray DW, Gill HS  2010 Mar 22

Original Link  http://www.ncbi.nlm.nih.gov/pubmed/20334994?dopt=AbstractPlus

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.

In 11 patients, the oxygenation was measured in the superolateral quadrant of the femoral head during resurfacing with a modified posterior approach, designed to preserve the blood supply, using a gas-sensitive electrode. These were compared with measures from 10 patients in whom the standard posterior approach was used. The modified approach patients maintained a significantly (P < .005) higher amount of relative oxygenation after the approach, 78% (standard deviation [SD], 45%) vs 38% (SD, 26%), and acetabular component implantation, 74% (SD, 56%) vs 20% (SD, 28%). The modified posterior approach, unlike the standard extended approach, does not significantly compromise the blood supply to the head; and we recommend this approach be considered for hip resurfacing.

Does commitment to rehabilitation influence the clinical outcome of total hip resurfacing arthroplasty study 2010

Link to original medical study

The purpose of this study was to evaluate whether compliance and rehabilitative efforts were predictors of early clinical outcome of total hip resurfacing arthroplasty.

Methods: A cross-sectional survey was utilized to collect information from 147 resurfacing patients, who were operated on by a single surgeon, regarding their level of commitment to rehabilitation following surgery. Patients were followed for a mean of 52 months (range, 24 to 90 months).

Clinical outcomes and functional capabilities were assessed utilizing the Harris hip objective rating system, the SF-12 Health Survey, and an eleven-point satisfaction score. A linear regression analysis was used to determine whether there was any correlation between the rehabilitation commitment scores and any of the outcome measures, and a multivariate regression model was used to control for potentially confounding factors.

Results: Overall, an increased level of commitment to rehabilitation was positively correlated with each of the following outcome measures: SF-12 Mental Component Score, SF-12 Physical Component Score, Harris Hip score, and satisfaction scores.

These correlations remained statistically significant in the multivariate regression model.

Conclusions: Patients who were more committed to their therapy after hip resurfacing returned to higher levels of functionality and were more satisfied following their surgery.

Author: David MarkerThorsten SeylerAnil BhaveMichael ZywielMichael Mont
Credits/Source: Journal of Orthopaedic Surgery and Research 2010, 5:20

Sports Activity After Total Hip Resurfacing Study 2010

Original Link http://www.ncbi.nlm.nih.gov/pubmed/20223940?dopt=Abstract

March 11, 2010

Banerjee M, Bouillon B, Banerjee C, Bäthis H, Lefering R, Nardini M, Schmidt J.
Dreifaltigkeits-Krankenhaus and Cologne Merheim Medical Center.

BACKGROUND: Little is known about sports activity after total hip resurfacing.

HYPOTHESIS: Patients undergoing total hip resurfacing can have a high level of sports activity. STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: The authors evaluated the level of sports activities with a standardized questionnaire in 138 consecutive patients (152 hips) 2 years after total hip resurfacing. Range of motion, Harris hip score, and Oxford score were assessed, and radiological analysis was performed.

RESULTS:  Preoperatively, 98% of all patients participated in sports activities. Two years postoperatively, 98% of the patients participated in at least 1 sports activity. The level of sports activity decreased after surgery. The number of sports activities per patient decreased from 3.6 preoperatively to 3.2 postoperatively. Intermediate- and high-impact sports, especially tennis, soccer, jogging, squash, and volleyball, showed a significant decrease while the low-impact sports (stationary cycling, Nordic walking, and fitness/weight training) showed a significant increase. Physical activity level at the time of follow-up as measured by the Grimby scale was significantly higher than in the year before surgery. Duration of sports participation per week increased significantly after surgery. Men had a significantly higher sport level than women before and after surgery. Eighty-two percent felt no restriction while performing sports. One-third missed certain sports activities such as jogging, soccer, tennis, and downhill skiing. The Harris hip and Oxford scores showed a significant increase postoperatively.

CONCLUSION: The results of this short-term follow-up study show that sports activity after total hip resurfacing surgery is still possible. Physical activity level increased with a shift toward low-impact sports. Duration of sports participation increased. High-impact sports activities decreased. These findings  can be important for the decision-making process for hip surgery and should be communicated to the patient.

Hospitals more specialized in orthopedic surgery show better outcomes for hip and knee replacement

 February 17, 2010  Click Here to read full article

A recent study of Medicare data by University of Iowa investigators indicates that hospitals with a higher degree of orthopedic specialization provide better outcomes for patients undergoing hip or knee replacement surgery.

The findings, which appear in the online version of the British Medical Journal, were based on a retrospective study of nearly 1.3 million Medicare beneficiaries aged 65 years and older who had hip or knee replacement procedures between 2001 and 2005 at 3,818 U.S. hospitals. The investigators grouped the hospitals into five categories according to their degree of orthopedic specialization. Orthopedic procedures accounted for 10.5% of admissions at the average hospital, while they represented 14.5% or more of the admissions in the most specialized group...

..."The findings suggest that more specialized hospitals have better outcomes even after we account for the type of patients each hospital cares for and the number of hip and knee replacement surgeries that each hospital performs," Tyson Hagen, MD, the lead author of the study, stated in the release...

Reference: Hagen TP, Vaughan-Sarrazin MS, Cram P. Relation between hospital orthopaedic specialisation and outcomes in patients aged 65 and older: retrospective analysis of US Medicare data. BMJ. Published online 2010 Feb 11.

Antibiotic Prophylaxis for Bacteremia in Patients with Joint Replacements by AAOS

February 2009 American Academy of Orthopaedic Surgeons

READ COMPLETE ARTICLE BY CLICKING HERE

This statement provides recommendations to supplement practitioners in their clinical judgment regarding antibiotic prophylaxis for patients with a joint prosthesis. It is not intended as the standard of care nor as a substitute for clinical judgment as it is impossible to make recommendations for all conceivable clinical situations in which bacteremias may occur. The treating clinician is ultimately responsible for making treatment recommendations for his/her patients based on the clinician’s professional judgment.

Any perceived potential benefit of antibiotic prophylaxis must be weighed against the known risks of antibiotic toxicity, allergy, and development, selection and transmission of microbial resistance. Practitioners must exercise their own clinical judgment in determining whether or not antibiotic prophylaxis is appropriate.

More than 1,000,000 total joint arthroplasties are performed annually in the United States, of which approximately 7 percent are revision procedures.1 Deep infections of total joint replacements usually result in failure of the initial operation and the need for extensive revision, treatment and cost. Due to the use of perioperative antibiotic prophylaxis and other technical advances, deep infection occurring in the immediate postoperative period resulting from intraoperative contamination has been markedly reduced in the past 20 years...

...Patients with joint replacements who are having invasive procedures or who have other infections are at increased risk of hematogenous seeding of their prosthesis. Antibiotic prophylaxis may be considered, for those patients who have had previous prosthetic joint infections, and for those with other conditions that may predispose the patient to infection. There is evidence that some immunocompromised patients with total joint replacements may be at higher risk for hematogenous infections. However, patients with pins, plates and screws, or other orthopaedic hardware that is not within a synovial joint are not at increased risk for hematogenous seeding by microorganisms...

...Given the potential adverse outcomes and cost of treating an infected joint replacement, the AAOS recommends that clinicians consider antibiotic prophylaxis for all total joint replacement patients prior to any invasive procedure that may cause bacteremia.

Thomas P. Gross, M.D. Midlands Orthpaedics p.a. Current status of uncemented femoral components in hip resurfacing Midlands Orthpaedics p.a.

 January, 2010

Uncemented femoral components for metal on metal total hip resurfacing have shown excellent results during the initial 3 years that I have been using this new technology. The early results that I have achieved in 0ver 800 cases since March 2007 are equivalent to the early results that I achieved with the same brand cemented femoral component.

Uncemented fixation of implants to bone is a proven technology that has generally surpassed the durability of cemented fixation to bone in traditional hip replacement surgery. In the long term (at 10 years) a higher percentage of hip implants using uncemented fixation still remain attached to the bone than cemented implants, especially in younger more active patients.

Fixation of total hip implants to bone can be accomplished by cement or by porous ingrowth technology (uncemented). Cement fixation is immediate. Cement is an acrylic material (methylmethacrylate) that is very brittle and also fairly toxic to bone cells. Cemented implants gradually loosen from the bone over time by reaction to the cement itself and due to gradual fatigue failure of this material. This process is faster in more active patients and faster in implant situations where the cement is stressed by shear forces rather than by compression forces.
 
Uncemented components are initially held to the bone by a very tight press-fit which is achieved by accurately preparing the bone so that the implant can be tightly hammered-on. The implants are so tightly wedged–on that the patient can bear full weight on them immediately. They do require a period of six to twelve months of bone ingrowth before they are considered well fixed. There is usually a small chance of failure of this bone ingrowth process in uncemented implants (<1%). But if ingrowth occurs, it is much more durable than cemented fixation and rarely fails in the long term.
 
Because orthopedic surgeons in America have come to a consensus on the superiority of uncemented fixation in total hips, uncemented fixation has virtually completely replaced cemented fixation in stemmed total hip replacements, despite the fact that these implants are more expensive. 99% of acetabular (socket) components that are used today are of the uncemented type, as are about 90% of femoral stems.
 
In hip resurfacing there is universal agreement that uncemented fixation is superior for the acetabular component. However, until recently, uncemented femoral components have not been available, therefore most hip resurfacing operations in the past have employed cemented fixation of the femoral component.
 
At the time that I began hip resurfacing in 1999, there was not yet general agreement that uncemented fixation was superior to cement in hip replacements. However, the evidence was mounting that uncemented fixation was better. I therefore did not think it was logical to use cemented fixation in hip resurfacing, an operation developed specifically with the more active younger patient in mind. The only companies pursuing hip resurfacing at the time were two small English companies: Corin and Midland Medical Technology (maker of the Birmingham implant). I suspect that they did not have the financial resources to develop a more complicated uncemented femoral component with the precision instrumentation required at that time. I originally proposed an uncemented femoral component to Corin 10 years ago, but they were unable to manufacture it at that time.
 
I therefore worked with Biomet on an uncemented femoral component and the precision instrumentation required for this implant for five years. I first began implanting it in March 2007. The Biomet component has a full coating of Titanium plasma spray under the entire under-surface of the femoral component. Recently we have added an additional layer of hydroxylappatite (HA) to increase the speed and extent of bone ingrowth. This is the best implant available to maximize the chance of bone ingrowth. When I started working with Biomet to develop an uncemented femoral component, Corin also started to work on one. They were able to bring it to market in Europe first; however, their component is only partially porous-coated (less than 50%) with Titanium (but it does have complete hydroxyl appetite coating). I personally do not believe this is good enough for long-term fixation (>10 years), but nobody knows for sure yet. It is not yet available in the US.
 
Theoretically, cement is the weak link when long-term (> 10 years) fixation of the femoral component is contemplated. If uncemented femoral components can be shown to achieve reliably high rates of ingrowth in the short term, they will probably outperform cemented femoral components in the long-term.
 
At this point with nearly 2-year follow-up data on a matched group of patients, I see no difference in results whether cement or uncemented fixation is used. At this point we can be fairly certain that bone ingrowth has occurred in these components. Except for two cases where osteonecrosis occurred in the femoral head at 1 year, we have had no failures of bone ingrowth in 430 patients that have are at least one year postop, and 191 that are at least two years postop.

In summary:

• Uncemented femoral resurfacing components are now available from BIOMET for any patient who desires them.
• No other companies are yet selling these in the US
• Corin has had an uncemented femoral component available in Europe for several years.
• At 2 years of follow-up there is no difference in the failure rate between cemented or uncemented femoral component.
• Uncemented fixation of implants is more durable at 10 years than cement in hip replacement surgery especially in young active patients.
• Most clinical data on hip surface replacement to date is based on an uncemented acetabular component and a cemented femoral component. 
• I now use uncemented components on virtually all hip resurfacing operations, unless the patient specifically requests the cemented femoral device. 

Thomas P. Gross, MD