Periprosthetic Femoral Fractures Linked to Bisphosphonates

Janis C. Kelly

October 09, 2018

Bisphosphonates have been linked to increased risk for atypical femoral fractures (AFFs), but the usual definition of AFF excludes periprosthetic femoral fractures (PFFs) in patients with hip or knee replacements.

Jean-Thomas Leclerc, MD, and colleagues from Centre Hospitalier Universitaire de Québec–Université Laval, Quebec City, Canada, have challenged that exclusion. In data reported online October 2 in Osteoporosis International, the researchers argue that atypical periprosthetic femoral fractures (APFFs) closely resemble common AFFs, that they account for 8.3% of all periprosthetic femoral fractures, and that this is clinically important because the role of bisphosphonates as a risk factor for APFF must be weighed against the benefits for osteoporotic patients.

"Our study showed that APFFs have characteristics distinguishing them from PFFs but similar to AFFs, such as transverse orientation of the fracture, periosteal reaction at the fracture, unicortical fracture, and prodromal symptoms. All the APFFs were minimally comminuted, occurred with low-velocity trauma, and showed a strong association with bisphosphonates. We believe that the ASBMR [American Society of Bone and Mineral Research] criteria for AFFs should reconsider the exclusion of periprosthetic fractures because they present similar characteristics and risk factors," the authors write.

Senior author Etienne L. Belzile, MD, told Medscape Medical News, "The take-home message is that previously, a periprosthetic femoral fracture was automatically excluded from possibly being related to bisphosphonate use. Now, those patients should be more closely reevaluated. In general, however, the incidence of atypical femoral fracture remains low, while the patient's benefits [from bisphosphonate treatment] outweighs the risk of fracture." Belzile is director of clinical and orthopaedic research at CHU de Québec, Université Laval, Quebec, Canada.

The researchers conducted a retrospective radiologic review of femoral fractures from 133 patients aged 18 years and older who had a PFF following a total knee replacement, total hip replacement, or hip hemiarthroplasty. APFF criteria included four of the following: transverse orientation; minimal comminution; periosteal thickening at the fracture; fracture of the lateral cortex only or of both cortices with a medial spike; or low-velocity trauma as cause.

The primary study objective was to establish the prevalence of APFFs among patients with PFF. A secondary objective was to identify characteristics of and risk factors for APFFs compared with PFFs.

The risk factor analysis included age, sex, body mass index, side of the fracture, tobacco use, velocity of the trauma, prodromal symptoms, a past history of fractures, level of autonomy, known diagnosis of osteoporosis or inflammatory arthritis, and overall health status according to the American Society of Anesthesiologists score. They defined low-velocity trauma as a fall from the patient's height, and high-velocity trauma as a fall from higher velocity mechanisms.

The researchers reviewed medical records for exposure to bisphosphonates, statins, proton pump inhibitors, and glucocorticoids. Prosthesis characteristics included type of arthroplasty, duration of implantation, evidence of previous loosening, number of surgeries on the joint prior to the fracture, whether the implant was cemented, and (for knee arthroplasties) degree of constraint of the prosthesis and presence of an intramedullary femoral stem.

There were 133 PFFs, of which 11 (8.3%) were APFFs. These included six hip arthroplasties and three knee prostheses; additionally, two patients had both arthroplasties. The APFFs occurred approximately 5 mm below the cement mantle or tip of the femoral stem.

The authors explain, "[W]e believe that both APFFs and PFFs mostly occurred around the stem because of the presence of an intramedullary implant that increased the mechanical stress and directed it to the femoral cortices, particularly at the tip of the stem. Moreover, in terms of the positioning of the stem, most of the APFFs (71.4%) and PFFs (39.4%) were positioned in varus. Varus positioning increases the stress on the lateral cortex and thereby the risk of PFFs. This increased tensile force on the lateral femoral cortex could contribute to APFFs in the same way as for the PFFs, but other factors such as bisphosphonate use could predispose the patient to an APFF."

There was no association between APFFs and knee arthroplasties. The authors suggest that APFFs of knee arthroplasties are "actually common AFFs of a femur on which a knee prosthesis was incidentally present, but without any association between the two."

The only clinical risk factors associated with significantly more APFFs were prodromal symptoms (45.5% vs 16.4%; P = .03) and exposure to bisphosphonates (72.7% vs 30.3%; P = .007). All eight of the bisphosphonate-exposed patients with APFF had taken alendronate (multiple brands); none had taken risedronate (multiple brands). Among the patients with PFF, 54.1% had taken alendronate, and 43.2% had taken risedronate .

The researchers also note that two meta-analyses ( Osteoporos Int. 2012 Jun;23:1823-34 and J Bone Joint Surg. 2005 Feb;87:293-301) showed beneficial effects of bisphosphonates on short-term periprosthetic bone preservation of hip and knee arthroplasties.

The authors write, "In the subgroup analysis, patients under 65 years of age with normal bone mineral density had the highest risk of fracture, in contrast to osteoporotic patients, for whom the risk was not increased. We believe that the benefits of bisphosphonates for osteoporotic patients with an arthroplasty outweigh the risks, but younger patients with long-term bisphosphonate therapy and an arthroplasty should be followed carefully."

Belzile said, "Clinically, vigilance is of the essence. If clinicians look for and take into account our findings, they will be more likely to identify a bisphosphonate user that could benefit from a change in medication. Patients developing an atypical femoral fracture are at risk of having one to the other leg, so stopping bisphosphonates and changing strategy (ie, class of medications) to treat their osteoporosis is important. This paper should change clinical practice. More research is required to better understand the patient's personal characteristics leading to one individual being more at risk of an atypical femoral fracture than another."

Dr Belzile and Dr Michou report multiple types of financial relationships with various companies. A full list of financial relationships is available on the journal's website. The remaining authors have disclosed no relevant financial relationships.

J Bone Mineral Res. Published online October 2, 2018. Abstract

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