The Benefits Of Bisphosphonate Therapy Have Been Shown To Extend Beyond The Recommended Treatment Protocol
Study finds that very infrequent dosing of zolendronate prevents bone loss over 11 years.
IV Bisphosphonate Therapy for Osteoporosis in Older Women: How Slow Can You Go?
by Darius Schneider, MD, PhD
In osteoporosis, osteoclast and osteoblast activities are discordant -- bone resorption happens at a faster rate than bone buildup, making bones fragile (porous) and increasing fracture risk, especially in postmenopausal women. In people with osteoporosis, even an inconspicuous trauma can result in a fragility fracture -- most times the first symptom of this otherwise dangerously silent condition. After experiencing the first fracture, the likelihood of incurring another greatly increases. A fracture can necessitate months of rehabilitation therapy and can lead to permanent debilitation. Hip fractures in particular are linked to the loss of independent living and an elevated risk of premature death, whereas vertebral fractures are strong predictors for additional future fractures.
Despite the deleterious effects of osteoporotic fractures, osteoporosis is massively undertreated, at great human and socioeconomic cost: up to 85% of women who suffer fragility fracture due to osteoporosis do not receive treatment to protect against further disabling and potentially life-altering fractures (IOF data).
This is especially surprising, since we have excellent therapies to reduce substantially the risk of osteoporotic fractures. One of the therapeutic options that has been around for decades are bisphosphonates. BPs are antiresorptive agents acting on osteoclast activity. They have been extensively shown to both halt bone loss and lower fracture risk, and are considered a safe first-line treatment for many forms of osteoporosis. Common side effects include GI upset and GERD, and, when given intravenously, self-limiting flu-like symptoms. But it is the extremely rare side effects of "osteonecrosis of the jaw" and "atypical fractures of the femur" that have recently led to a concerning treatment hesitancy towards this class of medication. In fact, according to a 2015 report in the Journal of Bone and Mineral Research, the rate of BP use fell by half from 2008 to 2018.
While BPs should be used judiciously, maybe more so than other drug classes -- and I personally strongly advocate a maximum of 5 years of use -- there is no reason to demonize these useful medications altogether.
Under these auspices, it is very helpful to learn from a study published in the Journal of Clinical Endocrinology & Metabolism, that intravenous BPs may be given at much wider intervals than previously assumed, without losing their bone protective activity. This is not surprising: BPs -- unlike newer antiresorptive agents (denosumab, romosozumab) -- are embedded into the bone structure, from which they are slowly released during bone remodelling, therefore continuing to act for many years after their discontinuation. This information -- hopefully soon backed by data showing that the effect on fracture reduction is, at least partially, preserved also -- may help increase treatment willingness in both hesitant patients and physicians, and provide clinicians and patients with one more tool to improve treatment adherence.
Darius Schneider, MD, PhD, practices endocrinology in La Jolla, California.