Bisphosphonates Show No Significant Benefit for Hip Fracture Risk after Five Years

January 19, 2021
Ingrid Torjesen

Dr Joan Lo, MD, a research scientist with the Kaiser Permanente Northern California Division of Research, said: “We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after five years or stayed on the medication for 10 years. Whether there is a benefit to staying on the drug for seven years needs to be further studied in randomized trials.”

Continuing bisphosphonates for an additional five years after an initial five years of treatment does not reduce the risk of hip fracture, however continuing it for two more years may provide some benefits, suggests a study published on JAMA Network Open1.

Bisphosphonate drugs are the first-line therapy for osteoporosis and there is strong evidence to support their use for three to five years2. They are then usually discontinued because the benefits of continuing therapy are uncertain.

To examine whether there are any benefits from continuing therapy beyond this point, researchers conducted a retrospective study using data from electronic health records of Kaiser Permanente members in Northern and Southern California. They included data on 29,685 female patients who initiated oral bisphosphonate therapy with alendronate, risedronate, or ibandronate between January 1, 1997 and September 30, 2009 and had received treatment for at least five years. At this point patients either discontinued therapy or continued it for an additional two or five years, and all were monitored for hip fracture for five years. A six-month grace period was allowed for discontinuation of therapy.

Dr Joan Lo, MD, a research scientist with the Kaiser Permanente Northern California Division of Research, said: “We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after five years or stayed on the medication for 10 years. Whether there is a benefit to staying on the drug for seven years needs to be further studied in randomized trials.”

A total of 507 hip fractures were recorded during the five years of follow up. Analysis of the data revealed that compared with discontinuing bisphosphonates, there were no differences in the cumulative incidence of hip fracture if women remained on therapy for two or five additional years (five-year risk difference [RD], −2.2 per 1000 individuals; 95% CI, −20.3 to 15.9, and 5-year RD, 3.8 per 1000 individuals; 95% CI, −7.4 to 15.0 respectively).

While five-year differences in hip fracture risk were not significantly different between continuation for five additional years compared with continuation for only two additional years (five-year RD, 6.0 per 1000 individuals; 95%CI, −9.9 to 22.0), results for interim hip fracture risk suggested that there may be a small potential benefit from continuing for an additional two years. Interim hip fracture risk appeared lower if women discontinued after two additional years (three-year RD, 2.8 per 1000 individuals; 95% CI, 1.3 to 4.3 and four-year RD, 9.3 per 1000 individuals; 95% CI, 6.3 to 12.3) but only when the six-month grace period was used to define discontinuation as this allowed the inclusion of a greater number of women.

Dr Lo emphasized that the study only looked at hip fracture and did not focus on patients with specific rheumatologic disorders who may be at higher risk for fracture. “The optimal duration of osteoporosis treatment remains unclear. Many experts recommend an assessment after five years of treatment, with discontinuation of therapy for those with a lower fracture risk,” she explains. “Future clinical trials should examine whether there is a benefit of two additional years of treatment after the first five years (ie, seven years total) and the optimal treatment interval for higher risk populations also needs to be studied.”

All women included in the study were at least 60% adherent to bisphosphate treatment in each of the five years after treatment initiation, according to dispensing data. Women were excluded from the study if they had previously received intravenous bisphosphonate or etidronate, or taken denosumab, teriparatide, raloxifene, or oestrogen in the past two years prior to the index date. They were also excluded if they had advanced or end-stage kidney disease (a metabolic bone condition), secondary or metastatic cancer, or multiple myeloma.

References

1. Izano MA, Lo JC, Adams AL, et al. Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women. JAMA Netw Open. 2020;3(12):e2025190. Published 2020 Dec 1. doi:10.1001/jamanetworkopen.2020.25190

2. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis [published correction appears in Osteoporos Int. 2015 Jul;26(7):2045-7]. Osteoporos Int. 2014;25(10):2359-2381. doi:10.1007/s00198-014-2794-2