What are the treatment options for osteoporosis in a patient with a hip fracture who is already on bisphosphonate (bone resorption inhibitor) therapy?

From the Guidelines

For a patient with a hip fracture who is already on bisphosphonate therapy, treatment should focus on optimizing fracture healing while addressing the underlying osteoporosis, and the most effective approach is to temporarily discontinue the bisphosphonate and consider switching to an anabolic agent such as teriparatide or romosozumab for 12 months, as supported by the latest evidence from 1. This approach is based on the latest study from 1, which found that bisphosphonates and denosumab reduce hip fracture risk, and that the sequential use of romosozumab followed by alendronate is more effective than alendronate alone in reducing hip fracture risk. The treatment plan should include:

• Ensuring surgical fixation or replacement of the hip fracture as appropriate
• Temporarily discontinuing the bisphosphonate and considering switching to an anabolic agent such as teriparatide (Forteo) 20 mcg subcutaneously daily or romosozumab (Evenity) 210 mg subcutaneously monthly for 12 months to stimulate bone formation
• Ensuring adequate calcium intake (1000-1200 mg daily) and vitamin D supplementation (800-1000 IU daily) with a goal 25-hydroxyvitamin D level of at least 30 ng/mL
• Resuming antiresorptive therapy with either the previous bisphosphonate or considering denosumab (Prolia) 60 mg subcutaneously every 6 months as an alternative after completing the anabolic therapy course
• Implementing fall prevention strategies, physical therapy for gait training, and balance exercises once the fracture has sufficiently healed. The American College of Physicians guideline update from 1 also recommends offering pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women with known osteoporosis. However, the most recent and highest quality study from 1 provides the strongest evidence for the treatment approach, and its findings should be prioritized in clinical decision-making.

From the FDA Drug Label

The efficacy and safety of Prolia in the treatment of patients with glucocorticoid-induced osteoporosis was assessed in the 12-month primary analysis of a 2-year, randomized, multicenter, double-blind, parallel-group, active-controlled study Patients were randomized (1:1) to receive either an oral daily bisphosphonate (active-control, risedronate 5 mg once daily) (n = 397) or Prolia 60 mg subcutaneously once every 6 months (n = 398) for one year.

Treatment options for osteoporosis in hip fracture patients already on bisphosphonates:

• Denosumab (Prolia): may be considered as an alternative treatment option for patients with osteoporosis who are already on bisphosphonates, as it has been shown to increase bone mineral density (BMD) in patients with glucocorticoid-induced osteoporosis compared to bisphosphonates 2.
• Bisphosphonates: may still be effective in patients with osteoporosis, but the addition of denosumab may provide additional benefits in terms of BMD increase 2. It is essential to note that the long-term consequences of using denosumab are unknown, and its effects on bone remodeling rates are still being studied 2.

From the Research

Osteoporosis Treatment Options in Hip Fracture Patients on Bisphosphonates

• Bisphosphonates are effective in preventing future hip fractures, but some patients may experience delays in treatment initiation or discontinuation of treatment 3.
• Factors associated with delayed dispensing of bisphosphonates include older age, male sex, and anxiety, while factors associated with early discontinuation include previous falls and female sex 3.
• The risk of atypical femur fractures (AFFs) increases with longer bisphosphonate duration, and other risk factors for AFFs include Asian ancestry, short stature, overweight, and glucocorticoid use 4.

Predictors of Hip Fracture Despite Bisphosphonate Treatment

• Predictors of hip fracture despite bisphosphonate treatment include age 75 years or older, female sex, white race, and low body mass index 5.
• Independent ability to transfer and occasional urinary incontinence are also important predictors of hip fracture despite bisphosphonate treatment 5.
• Targeting fracture prevention efforts beyond pharmacologic therapy to include existing nonpharmacologic therapies, such as fall prevention strategies, may be beneficial 5.

Bisphosphonate Treatment Duration and Hip Fracture Risk

• The efficacy of continuing bisphosphonate treatment beyond 5 years is uncertain, and the risk of hip fracture does not differ significantly between women who discontinue treatment and those who continue treatment for 5 additional years 6.
• Discontinuing bisphosphonate treatment after 2 additional years may be associated with a lower risk of hip fracture compared to continuing treatment for 5 additional years 6.

Comparative Effectiveness of Drug Treatments for Fragility Fractures

• Teriparatide, bisphosphonates, and denosumab are the most effective drugs in reducing the risk of fragility fractures, although differences in efficacy across drugs are small 7.
• Calcium and vitamin D are ineffective in reducing the risk of fragility fractures when given separately, but may be effective when given in combination 7.