1. I know that hip fractures are bad, but once a patient has had one, why worry about osteoporosis treatment? Isn't the horse already out of the barn?

While hip fractures are the most serious and debilitating fracture from osteoporosis, there is now evidence that the fractures are associated with a significant risk of subsequent fracture in both men and women, and in both African-Americans and Caucasians. Such fractures occur at a rate of 10.4 per 100 patient years, which is 2.5 times as high as the rate in age-matched persons without a hip fracture.

A large meta-analysis showed that peri- and postmenopausal women with prior fractures had 2.0 (95% CI=1.8-2.2) times the risk of a subsequent fracture compared to women without prior fractures. In other studies (that included women and men) the risk was increased 2.2 (1.9-2.6) times. Finally, a study of nursing home residents showed that those with a prior hip fracture were 2.99 (2.78-3.21) times more likely to have a subsequent fracture compared to those residents without a fracture. Thus, patients who have a hip fracture have a major risk of subsequent fractures and should be evaluated and considered for therapy to reduce their risk of further fractures unless comorbid conditions preclude treatment or the patient has a life expectancy of less than 1 year.

2. Can anything be done to reduce the fracture risk after a person has had a hip fracture?

Yes, a clinical trial has demonstrated that men and women with surgical repair of a low-trauma hip fracture treated within 90 days of the surgical repair who receive 5 mg zoledronic acid intravenously annually have a 35% reduction in the risk of subsequent clinical fractures. Since hip fracture patients have such low 25-hydroxyvitamin D levels all patients received 50,000-125,000 IU of vitamin D2 or D3, orally or intramuscularly 14 days before receiving zoledronic acid.

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3. Before beginning osteoporosis therapy after a hip fracture, what studies should a patient have?

Before administering zoledronic acid to patient with a hip fracture most clinicians perform a serum 25-hydroxyvitamin D level to make sure that it is at least 25 ng/ml. In addition, a serum calcium level should be normal and the patient should have a glomerular filtration rate of 35cc/min or greater. The patient should also be advised that over 30% of people who receive an intravenous bisphosphonate without having had any prior exposure to the drug may develop a flu-like illness within 6-24 hours after receiving the medication. This response is expected and usually lasts only 24-48 hours. Aspirin, acetaminophen or ibuprofen can mitigate the symptoms.

4. The HORIZON Recurrent Fracture Trial showed a significant effect of zoledronic acid on mortality in patients who had surgical repair of their low-trauma hip fracture. Has this study been replicated?

In the HORIZON Recurrent Fracture Trialthere was a 28% reduction in mortality from any cause. A post hoc analysis of the trial data showed that only 8% of the zoledronic acid death benefit was due to fracture reduction. Zoledronic acid-treated patients were less likely to die from arrhythmias and pneumonia than placebo-treated subjects and there were similar incidences of both illnesses in both treated and control patients.

While the evidence from clinical trials is best for zoledronic acid for reducing mortality in patients with a hip fracture, meta-analyses and population studies suggest that the mortality benefit also occurs with oral bisphosphonates as well as denosumab and strontium, when used to treat patients with osteoporosis. Two additional studies suggest that oral bisphosphonates reduce the incidence of myocardial infarctions when used to treat osteoporosis . Clearly this is an area that warrants further investigation to better understand the diseases affected and the mechanism(s) of action of these agents in reducing mortality.

What’s the Evidence?/References

Colon-Emeric, C, Kuchibhatla, M, Pieper, C.. “The contribution of the risk of hip fracture to subsequent fracture: data from two longitudinal studies”. Osteoporosis Int. vol. 14. 2003. pp. 879-83.

Klotzbuecher, C, Ross, PD, Landsman, PB. ” Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis”. J Bone Minerl Res. vol. 15. 2000. pp. 721-39.

Lyles, KW, Schenck, AP, Colon-Emeric, CS. “Hip Fractures and other osteoporotic fractures increase the risk of subsequent fractures in nursing home residents”. Osteoporosis Int. vol. 19. 2008. pp. 1225-33.

Lyles, KW, Colon-Emeric, CS, Magaziner, JS. “Zoledronic acid and clinical fractures and mortality after hip fracture”. N Engl J Med. vol. 357. 2007. pp. 1799-809.

Pieper, CF, Colon-Emeric, CS, Caminis, J. “Distribution and correlates of serum 25-hydroxyvitamin D levels in a sample of patients with hip fracture”. Amer J Geriatric Pharm.. vol. 5. 2007. pp. 335-40.

Colon-Emeric, CS, Mesenbrink, P, Lyles, KW. “Potential mediators of the mortality reduction with zoledronic acid after hip fracture”. J. Bone Minerl Res. vol. 25. 2010. pp. 91-7.

Grey, A, Boland, MJ. “The effects of treatments for osteoporosis on mortality”. Osteoporosis Int. vol. 24. 2013. pp. 1-6.

Kang, J-H, Keller, JJ, Lin, H-C. “Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study”. Osteoporosis Int. vol. 24. 2013. pp. 271-7.

Wolfe, F, Bolster, MB, O’Connor, CM. “Bisphosphonate use is associated with reduced risk of myocardial infarction in patients with rheumatoid arthritis”. J Bone Minerl Res. 2012.