Effect of Bisphosphonate Initiation at Week 2 Versus Week 12 on Short-Term Functional Recovery after Femoral Neck Fracture: a Randomized Controlled Trial.

Shawn Yee, Mercer University College of Pharmacy

Hip fractures in the elderly population are associated with serious health consequences, which includes significant mortality, loss of mobility, and decreased independence. [1,2] Bisphosphonates are the most commonly used medications for osteoporosis treatment and prevention. [3,2] They work by inhibiting bone resorption and causing osteoclast apoptosis. [4,2] However, due to concerns with correcting low vitamin D and calcium levels as well as potentially negative effects on healing, the appropriateness of early treatment initiation of bisphosphonates is unclear. [5,2]

A recent meta-analysis (N= 10 trials, N= 2,888) that reviewed early versus late initiation of bisphosphonates after surgery for fractures found that fracture healing time was not delayed with early initiation of bisphosphonates. The included studies used alendronate, zoledronic acid, risedronate, and etidronate. [6] Below is a summary of a randomized controlled trial evaluating the effects of early versus late initiation of risedronate post-hemiarthroplasty. [2]

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Protection from Osteoporosis for Two Years with One Shot?

The balance between collagen and mineral components that make up bone is delicate to maintain bone strength and stiffness. Imbalances in these components can impair bone quality and reduce strength, leading to osteoporosis. Increasing bone mass decreases bone fracture risk. Bone mass can be increased by modifying lifestyle factors or by medication administration.1

Zoledronic acid (Reclast®, Zometa®) is a bisphosphonate indicated by the Food and Drug Administration (FDA) for postmenopausal, male, and glucocorticoid-induced osteoporosis. Bisphosphonates decrease osteoclast maturation, number, recruitment, bone adhesion, and lifespan and indirectly increase bone mineral density. Zoledronic acid is administered intravenously (IV) and is 40% excreted, compared to 50-65% of other oral bisphosphonates. Zoledronic acid also has fewer gastrointestinal side effects and is used in patients who have intolerances to oral bisphosphonates.1

The American College of Obstetricians and Gyencologists’ guidelines for osteoporosis recommend any FDA-approved therapy be used including raloxifene, bisphosphonates, parathyroid hormone, denosumab, or calcium. No treatment algorithm or preferential treatment is suggested.2 The Medical Services Commission recognizes that bisphosphonates have the largest body of randomized controlled trial evidence of all therapies in osteoporosis. However, cost effectiveness is low with zoledronic acid and it is therefore recommended to be reserved for high-risk patients unable to tolerate oral therapy.3

According to the University of Michigan Health System guidelines, the World Health Organization’s Fracture Risk Assessment Tool (FRAX) should be used to assess the need for treatment. Medication is recommended to begin in patients with 10-year fracture risks greater than 3% at the hip or 20% total. Zoledronic acid is only recommended to reduce hip and vertebral fracture risk in post-menopausal women and glucocorticoid-induced osteoporosis.4

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