Osteoporosis Drugs May Help Oldest, Sickest Women Most

Veronica Hackethal, MD

June 18, 2019

Frail, very elderly women with osteoporosis may benefit the most from osteoporosis drugs, according to a study published online yesterday in JAMA Internal Medicine.

Women older than 80 years with osteoporosis and multiple medical problems or poor prognosis had more than triple the risk for hip fracture in the next 5 years, compared with women in the same age group who had increased fracture risk but no osteoporosis.

Approximately 33% of women who live to age 90 years will suffer a hip fracture, which is associated with functional decline, nursing home placement, and death.

But this age group often has multiple medical problems that can complicate management with osteoporosis drugs. Some doctors may be concerned that the risks of prescribing these medications outweigh the benefits in individuals with a limited life span.

"Clinicians should consider the initiation of drug treatment to prevent fracture in late-life women with osteoporosis (bone mineral density [BMD] T-score -2.5 or below) and multiple comorbidities, as this group of women may derive the greatest absolute benefit of treatment in preventing future hip fractures," author Kristine Ensrud, MD, MPH, University of Minnesota, Minneapolis, told Medscape Medical News.

She added that women aged 80 years and older should also be counseled about the risk for hip fracture and considered for osteoporosis screening, even if they have multiple medical problems and limited life expectancy.

In a linked editorial, Sarah D. Berry, MD, MPH, Sandra Shi, MD, and Douglas P. Kiel, MD, MPH, all from Harvard Medical School, Boston, Massachusetts, seem to agree.

"If medications to prevent fracture are equally effective in older women with multiple comorbidities as they are in younger women, then older women with comorbidities are the individuals most likely to benefit from osteoporosis treatment," they write.

Although the editorialists emphasize the results concerning frail, very elderly women with osteoporosis, Ensrud said the results for very elderly women without osteoporosis are also important.

"Both results have clinical relevance," she explained. "The results suggest that drug treatment in the first group of women (those with osteoporosis) may be an example of high value care, while drug treatment initiation in the second group (those without osteoporosis but considered drug candidates by the National Osteoporosis Foundation) may be an example of low value care."

The distinction is important because expanded indications for osteoporosis diagnosis and/or treatment have recently been proposed by the National Osteoporosis Foundation and National Bone Health Alliance (NBHA). Doing so may increase the number of patients eligible for osteoporosis drugs. But according to these results, the absolute benefit of treatment may be lower for some of these individuals.  

Currently, very little evidence supports the efficacy of osteoporosis medications in very elderly women, because many randomized controlled trials have excluded this group. However, accumulating evidence from post-hoc analyses and relatively small studies in nursing homes has suggested that osteoporosis drugs are probably effective in this group.

Current professional guidelines recommend osteoporosis treatment in individuals over age 50 with clinical signs of osteoporosis (BMD T-score of -2.5 or lower, vertebral fracture, or hip fracture). But these guidelines offer no guidance regarding extreme age, multiple medical problems, or frailty.

"[W]ell-designed observational studies are essential to evaluate the efficacy and safety of osteoporosis medications in this rapidly growing patient population," Ensrud said.

More research is also needed to develop better fracture prediction models that take into account risk for death and multiple medical problems in very elderly patients.

The researchers analyzed data from a subgroup of the Study of Osteoporotic Fractures, a prospective cohort study that began recruiting in 1986. The larger study included 9704 white women ages 65 and older who were able to walk unassisted; the women lived in four regions of the United States. 

From 2002 to 2004, women in the larger study were invited to participate in the 16-year study. The analysis included 1528 of these women who had never received osteoporosis drugs. Women completed questionnaires every 4 months about lifestyle, health status, past falls, 14 medical conditions, and ability to perform activities of daily living. The women also received clinical examinations, including measurement of BMD.  Participants had a mean age of 84.1 years and a mean BMD t-score at the femoral neck of -2.24; 17.9% (n = 274) had three or more medical conditions and 4.3% (n = 66) had a poor prognosis.

The investigators separated women into groups on the basis of the NBHA definition of osteoporosis (BMD T-score of -2.5 or lower, vertebral fracture, or hip fracture): those with osteoporosis (n = 761) and those without osteoporosis who nonetheless had high risk for fracture (n = 767). (At risk for fracture but without osteoporosis was defined according to expanded NBHA criteria for osteopenia.)

They estimated 5-year risk for osteoporotic hip fracture using the Fracture Risk Assessment (FRAX) tool, a computer-based algorithm that uses clinical risk factors and country-specific data. They estimated prognosis using the Lee Index, a validated mortality prediction index.

Over a maximum follow-up of 5 years, 8% (n = 125) had a hip fracture, whereas 18.8% (n = 287) died before having a hip fracture.

Women with osteoporosis had a probability of dying during the next 5 years of 24.9% (95% confidence interval [CI], 21.8 - 28.1). This probability was 19.4% (95% CI, 16.6 - 22.3) in women without osteoporosis but with high fracture risk.

Analyses that took into account the competing probability of death showed that women with osteoporosis had a 5-year hip fracture probability of 13% (95% CI, 10.7 - 15.5). This probability was 4% (95% CI, 2.8 - 5.6) among women without osteoporosis but at high fracture risk.

Regardless of whether or not they had osteoporosis, women had increased probability of dying if they had more comorbidities and worse prognosis.

However, having osteoporosis and multiple medical conditions greatly increased the probability of hip fracture during those 5 years and the probability further increased as medical conditions increased or prognosis worsened.

For example, women with osteoporosis and three or more medical conditions had a 5-year probability of hip fracture of 18.1% (95% CI, 12.3 - 24.9). Among women without osteoporosis who were at high risk for fracture, those who had three or medical conditions had a 2.5% (95% CI, 1.3 - 4.2) probability of hip fracture over 5 years.

The study included noninstitutionalized white women, so results may not apply to women of other races/ethnicities, men, or people in facilities such as nursing homes.  

The study was supported by National Institutes of Health funding and the National Institute on Aging (NIA), and the Minneapolis VA Health Care System. One or more authors report receiving royalties and/or grant support from one or more of the following: UpToDate, Merck & Co, and/or NIH. The remaining authors have disclosed no relevant financial relationships.

Berry reports royalties from UpToDate (Wolters Kluwer). Kiel reports royalties from UpToDate (Wolters Kluwer), grants from the Dairy Council, grants from Radius Health, and personal fees from Springer. Shi has disclosed no relevant financial relationships.

JAMA Int Med. Published online June 17, 2019. Abstract, Editorial

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