Denosumab is administered as a 60-mg subcutaneous injection every 6 months.
Randomized trial #1. Denosumab led to greater increases in bone density than oral alendronate. In a comparison of denosumab and alendronate, 1,189 postmenopausal women who had osteoporosis were randomized to treatment with subcutaneous denosumab, 60 mg every 6 months, or oral alendronate 70 mg a week for 1 year.
After 1 year of treatment, denosumab produced a significantly greater increase in bone density than alendronate did (at the lumbar spine, 5.3% compared to 4.2%, respectively; at the hip, 3.5% and 2.6%).1
Randomized trial #2. Directly relevant to the case of Ms. Clark, denosumab has been demonstrated to be effective for treating postmenopausal women treated previously with alendronate. Five hundred postmenopausal women taking alendronate, 70 mg weekly, were randomized to 1) stop alendronate and start denosumab or 2) continue alendronate therapy.
After 12 months of treatment, BMD increases were significantly greater in the women receiving denosumab than in those receiving alendronate at the hip (1.9% compared to 1.0%, respectively) and lumbar spine (3.0% and 1.8%).2
Last, in addition to improving BMD, denosumab, in comparison to placebo, has been demonstrated to reduce the rate of fractures of the hip (by 40%) and lumbar spine (by 68%) and of nonvertebral fractures (by 20%), such as the wrist.3
Zoledronic acid
At a dosage of 5 mg annually by IV infusion, zoledronic acid improves BMD and decreases the risk of fracture.
Randomized trial. 7,765 postmenopausal women who had osteoporosis were randomized to annual IV infusion of 5 mg of zoledronic acid or placebo for 3 years. Over 3 years of treatment, zoledronic acid, compared with placebo, was associated with a reduced rate of vertebral (3.3% compared with 10%, respectively) and hip fractures (2.5% and 1.4%).5
Practical matters
Zoledronic acid must be administered as an IV infusion over at least 15 minutes; rapid administration can damage renal glomeruli and result in renal dysfunction. Renal damage can be avoided by 1) infusing zoledronic acid slowly and 2) ensuring that the patient is hydrated before beginning.
ObGyn practices do not routinely administer “prolonged” IV infusion of medications, however. Committing resources to develop an infusion service may therefore not be an optimal use of limited resources in an ObGyn practice.
An alternative to IV infusion of zoledronic acid is subcutaneous administration of denosumab. Given that drug’s ease of use, it appears singly suited for use in an ObGyn generalist’s practice.
CASE: Plan put in action
Ms. Clark underwent reconstructive wrist surgery. She also started denosumab treatment as an every-6-month subcutaneous injection. Her physicians await the results of the next bone density test.
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