Marlene Busko

October 21, 2015

SEATTLE — In a new observational study of older women in Scotland who had a fracture, those who also received an oral bisphosphonate as opposed to only calcium and vitamin D supplements were less likely to have another fracture or die during an 8-year follow-up.

But in another study in a large cohort of older women in northern California who were taking oral bisphosphonates, Asians (mainly Chinese and Filipinos) were more likely than whites to have a rare subtrochanteric or femoral shaft fracture (atypical femur fracture).

The two studies were presented as late-breaking trials at the recent American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

In the study from Scotland, after researchers corrected for the worse baseline risk factors, women who received bisphosphonates had a lower risk of having another fracture (hazard ratio [HR], 0.59) or dying (HR, 0.79) during follow-up, Tineke van Geel, MD, PhD, from Maastricht University, the Netherlands, reported.

"There's a lot of evidence…that having osteoporosis, losing bone, and having fractures are all associated with an increased risk of mortality," study coauthor John Eisman, MBBS, PhD, from the Garvan Institute of Medical Research, in Sydney, Australia, told Medscape Medical News.

"What these data say is that these people [with a fracture]…we know they are more likely to die, we know they are not [always] being treated [with osteoporosis-prevention therapies]; but if they are treated, they are more likely to survive," he said. "That is absolutely astonishing."

In the study of women in California, Asian women who received oral bisphosphonates were older and took bisphosphonates for a longer time than white women (3.8 years vs 2.7 years). However, after adjustment for this, Asians had about a sevenfold higher risk of having an atypical femur fracture.

Thus, "when counseling Asian women regarding long-term bisphosphonate therapy, we should inform them of a potential increased risk of an atypical femur fracture," Joan C Lo, MD, from Kaiser Permanente Northern California Division of Research, Oakland, said.

However, Dr Eisman cautioned that atypical fractures are very rare. And for every atypical fracture, oral bisphosphonates would have prevented 100 hip fractures and probably 1000 other fractures, he stressed.

8-Year Oral Bisphosphonate Study

Breaking a bone increases a person's risk for having a second fracture and possibly dying sooner, Dr van Geel explained. The researchers aimed to examine the effect of oral bisphosphonates on subsequent fractures and mortality during 8 years of follow-up.

They invited 9439 men and women over age 50 who sustained a fracture during 1999–2007 to be assessed by the Glasgow Fracture Liaison Service. A total of 5011 patients (53.1%) who were not too frail and not receiving therapy for osteoporosis agreed to be assessed.

All patients received calcium and vitamin D therapy. About half (2534 patients, 50.7%) were prescribed oral bisphosphonates because they met the cutoffs for older age and poor bone-mineral-density scores. These patients also had a worse fracture type (eg, a hip fracture vs a finger fracture).

A total of 11.8% of patients who received only calcium and vitamin D therapy and 13.3% of the patients who also received bisphosphonates had a subsequent fracture during follow-up (P = .126).

Patients who received bisphosphonates had a higher absolute risk of dying during follow-up (15.0% vs 9.5%, P < .001). However, these patients also had a worse baseline risk profile for age (mean age, 73.4 vs 64.4), hip fracture (21.7% vs 6.2%), and bone-mineral density (T score, -3.1 vs -1.5), although they were more likely to be female (82.9% vs 72.4%), which is protective against fractures.

Age, gender, bone-mineral density, fracture location, alcohol intake, glucocorticoid use, and smoking all predicted a greater risk of subsequent fractures and death during follow-up.

After adjustment for these other risk factors, patients who had been prescribed bisphosphonates had a lower risk of a subsequent fracture and a lower mortality risk (that was not attributable to fewer subsequent fractures).

"Typically, women leaving the hospital in the US [after being hospitalized for a fracture], maybe 25% now get investigated and/or treated for osteoporosis, and it's like that [or worse] around the world, and for men it's certainly worse," Dr Eisman said.

"This [study] is saying that these treatments, which are still incredibly poorly applied in most places, are in fact having substantial improvements in mortality."

Risk of Rare Fractures in Asians vs Whites

Meanwhile, Dr Lo explained that several epidemiologic studies have suggested that Asian women are more prone than white women to have a rare, atypical femur fracture when taking bisphosphonate therapy.

She and her colleagues examined data from 48390 women age 50 and older who were insured by Kaiser Permanente and started receiving oral bisphosphonate therapy during 2002–2007.

The women had a mean age of 69.5, and 65.3% were white, 17.1% were Asian, and 17.6% were other races (ie, 9.5 % Hispanic, 4.1% black, and 4.0% other or unknown race)

During a median follow-up of 7.7 years, 68 women who had received bisphosphonates for a median of 5.5 years had an atypical femur fracture.

More than half of the women with an atypical femur fracture were Asian: 60.3% Asian, 26.5% white, and 13.2% other race.

The crude incidence of atypical femur fracture during follow-up (including periods on and off treatment) was 64.2 per 100,000 person-years in Asians vs 7.6 per 100,000 person-years in whites.

After correction for age, the risk of atypical femur fracture was 8.5-fold higher in Asians vs whites, and after adjustment for bisphosphonate use, it was 6.6-fold higher in Asians vs whites.

"Our study confirms marked racial disparity in atypical femur fracture risk that should be further examined, particularly the mechanisms accounting for this difference," Dr Lo and colleagues conclude.

The study from California was funded by the Kaiser Permanente Community Benefit Program and the National Institutes of Health. Dr Lo has received research support from Sanofi and Amgen. Dr van Geel has no relevant financial relationships.

American Society for Bone and Mineral Research 2015 Annual Meeting; Seattle, Washington. Abstracts LB1153 and LB1156, presented October 12, 2015.

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