Nancy A Melville

September 11, 2017

DENVER — The relatively simple measure of extending a routine dual X-ray absorptiometry (DXA) scan by 1 one minute may help identify patients at risk for atypical femoral fractures (AFF), a rare but potentially serious complication linked to bisphosphonate use.

At the same time, key characteristics identified in a separate population of patients with the fractures may also help determine those at risk, finds new work presented here at the American Society of Bone and Mineral Research (ASBMR) 2017 Annual Meeting.

"We found that an extended femur scan using DXA can identify incomplete atypical femoral fractures in patients using antiresorptive treatment [for osteoporosis]," said Denise Van de Laarschot, of the bone center, department of internal medicine, Erasmus MC, Rotterdam, the Netherlands, who presented one of the studies. "DXA is part of routine care, and extended scans can be easily implemented."

While atypical femoral fractures appear associated with long-term bisphosphonate use for osteoporosis, research regarding the causes remain unclear. Early detection, however, can at least allow for interventions to try to prevent a full atypical fracture.

By simply extending the regular length of a routine hip DXA scan — an effort that only takes about a minute longer than a standard scan — the entire femur can be depicted and screened for incomplete forms of AFF, Dr Van de Laarschot said.

AFF Can Be Present Without Pain

To determine the scientific utility of the measure, Dr Van de Laarschot and colleagues evaluated extended femur scans that were obtained on all patients already receiving DXA scans who had a history of bisphosphonate or denosumab use within the previous year.

Among patients showing signs of "beaking" or "flaring" — a localized periosteal or endosteal thickening of the lateral cortex — an X-ray of the femur was performed to confirm the presence of an incomplete atypical femoral fracture.

Of 282 patients evaluated, 12 (4.3%) showed signs of the beaking in extended scans of both femora.

In nine patients (3.2%), the beaking was found on X-ray to correspond with the presence of incomplete atypical femoral fractures. Four of the patients already had an X-ray performed due to a previous complete atypical femoral fracture in their other leg. Two patients were not available for follow-up.

Five of the patients (1.8%) were newly diagnosed to have six incomplete atypical femoral fractures that were not previously known, while the beaking in one patient was attributed to a false impression resulting from soft-tissue calcifications.

The positive predictive value of the presence of beaking on an extended femur scan was 83.3%, the authors reported.

One patient eventually required preventive surgery, and in all of the others the antiresorptive therapy was discontinued, Dr Van de Laarschot said.

"In summary, we identified 10 incomplete atypical femoral fractures in nine patients, with all cases showing beaking on the DXA," she noted.

Importantly, she added that only two of the nine patients with incomplete atypical femoral fractures had previously reported pain.

"This indicates that incomplete atypical femoral fracture can be present even in patients without pain."

The findings suggest the need for more extensive comparative analyses of costs and benefits with screening, Dr Van de Laarschot noted.

"We also need more prospective data to better understand how soon beaking may develop in these patients."

Method Doesn't Require Any Advanced Equipment

In the wake of reports of the atypical femoral fractures, as well as osteonecrosis of the jaw (ONJ), use of oral bisphosphonates has substantially declined, meaning many patients are not getting needed treatment, Dr Van de Laarschot explained.

"The fear of side effects like AFF and ONJ have likely led to a drastic decline in use of oral bisphosphonates of over 50% in just 4 years in the US," she said.

"We therefore desperately need a tool to identify those at risk of these adverse events, not only to timely diagnose incomplete AFF and possibly prevent complete fracture but also to restore faith in this very effective osteoporosis medication."

Coauthor Carola Zillikens, MD, PhD, of the department of internal medicine, Erasmus MC, said advanced equipment is not necessary to perform the scans.

"The method that we used does not require more advance scanning equipment and can be easily implemented using the normal DXA scanner by making an extended femur scan," Dr Zillikens told Medscape Medical News.

Dr Zillikens said their center started performing the extended scans in response to the increased AFF cases.

"We started to perform these scans because as a tertiairy referral center we see a lot of patients who have suffered from a complete AFF, with sometimes severe consequences. They often occur spontaneously, often in both legs, and often they do not heal well."

Canadian Study Identifies Five Characteristics That Up Risk of AFF

In the other study presented in the same session, Canadian researchers reported on the characteristics of 107 participants with AFF in the Quebec Atypical Femoral Fracture Registry, who were compared with cohorts including patients with other types of fractures and a cohort of bisphosphonate users.

In the 107 patients, who were 93% female, there were 161 AFFs, including 54 that were bilateral and 50 that were incomplete.

All of the participants were exposed to oral bisphosphonates, with an average cumulative duration of 10.4 years. Fewer than 4% were exposed to the drugs for less than 5 years, and the minimum exposure was 3.5 years.

Other key findings included that more than half of patients used proton-pump inhibitors (52%), 9% used hormone therapy, and 6% used raloxifene, all of which were used at a higher rate than in the general Quebec population.

X-ray 2D and 3D EOS scans that were available for 37 women confirmed varus anatomy at the hips and accentuated bowing of the femur, compared with a reference population.

The women had an average age of 69.5 years at the time of the AFF, and approximately 71% reported pain prior to the fracture.

Based on the findings, presenter Suzanne Morin, MD, an associate professor of medicine at McGill University, in Montreal, Quebec, said patients with the following characteristics may benefit from further examination with extended scanning or closer clinical follow-up:

  • Longer duration of therapy.

  • Use of concomitant medications, particularly proton pump inhibitors.

  • Femur bowing or varus at the hip.

  • Bone-mineral density in the osteopenic range.

  • Thigh or groin pain.

"Definitely, if there is thigh or groin pain, that should signal danger in these patients and should be evaluated promptly," Dr Morin said.

She told Medscape Medical News, "Our study adds to the body of evidence that femur geometry, concomitant use of proton-pump inhibitors, possibly a bone-mineral density in the osteopenic range, and the presences of groin or thigh pain are factors that may identify a subgroup of patients who are at a higher risk of developing AFFs in the setting of prolonged use of bisphosphonates (5 years or more)."

She added that "clinician- and patient-targeted knowledge dissemination strategies that address concerns about AFF and support optimal osteoporosis management are of paramount importance to achieve fracture risk reduction in clinical practice."

The authors had no relevant financial relationships.

American Society of Bone and Mineral Research 2017 Annual Meeting. September 8–11, 2017, Denver, Colorado.

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