Osteogenesis Imperfecta Into Adulthood: Does the Childhood Bisphosphonate Continue
A single patient whose bisphosphonate therapy has always been part of her life, started for a reason that no longer technically applies. The disagreement is whether continuing still helps, now that the specific problem it was started for is gone.
Wilhelmina G., a 24-year-old woman, has had osteogenesis imperfecta since birth — type IV — and started intravenous bisphosphonate therapy at age six after her third long-bone fracture in as many years, a treatment she and her parents credit with the dramatic reduction in fractures that followed. She is now a graduate student in library science, has broken only two bones since her early teens, both from what she describes as genuinely unlucky falls rather than the frequent minimal-trauma fractures that defined her early childhood, and has just transitioned from her longtime pediatric endocrinologist to an adult specialist for the first time.
That transition is what prompts the question in front of the group. She has been on zoledronic acid for eighteen continuous years, started specifically to reduce fracture risk during a period of rapid childhood growth that ended years ago. Her OI has not gone anywhere — it is a lifelong collagen disorder — but the rationale that originally justified the drug technically has. That distinction has real evidentiary weight rather than being a semantic one: nearly all the strong trial evidence behind bisphosphonates in OI, Glorieux and colleagues' original pamidronate work among it, enrolled children specifically to protect bone during active growth, and almost none of it was generated in skeletally mature adults. Eighteen years of cumulative exposure beginning in early childhood is also a materially different retention profile from the shorter courses studied in postmenopausal osteoporosis. Her lumbar spine T-score of −1.6 is the number that makes this genuinely open rather than rhetorical: it is not osteoporotic, and in a woman with type IV OI who has taken zoledronic acid since she was six, nobody can say whether that reflects eighteen years of drug effect that would decay without it, collagen that was always going to do reasonably well, or both in some proportion no scan distinguishes.
A rationale that outlasted the reason it started
I'd continue zoledronic acid. Her OI is a lifelong structural collagen disorder, not a childhood-limited condition — stopping just because her growth plates have closed conflates the original pediatric rationale, reducing fracture during rapid growth, with the ongoing adult one, reducing fracture from persistently abnormal bone quality. Those are different justifications that happen to use the same drug.
I'd want a monitored trial off therapy at this point. Nearly all of the strong trial evidence behind pediatric bisphosphonate use in OI — Glorieux and colleagues' original pamidronate trials among them — enrolled children specifically to protect bone during active growth. Almost none of that evidence base was generated in skeletally mature adults, and she's approaching two decades of cumulative exposure that started in early childhood, a genuinely different, less-studied retention profile than the shorter courses seen in postmenopausal osteoporosis.
I'm not disputing that OI itself is lifelong — I'm questioning whether continuing the same drug indefinitely is actually supported by adult-specific data, or whether we're extending a pediatric-trial-justified decision by inertia.
Her own fracture history doesn't actually settle this either way. A low fracture rate for the past several years on treatment is consistent with two different explanations: the drug is still working, or her OI has naturally entered a less fracture-prone adult phase independent of it. We can't tell those apart from her chart alone.
A monitored, closely-followed trial off therapy is the only way to actually distinguish which explanation is true — not a decision to stop permanently, but a real test, with a clear plan to resume if her fracture rate or bone turnover markers change.
Agreed: a monitored trial off zoledronic acid, with bone-turnover markers checked every six months and an explicit plan to resume therapy if those markers rise meaningfully or she sustains a new fracture, rather than continuing indefinitely by default or stopping without a defined monitoring plan.
Not fully settled: how long the trial should run before being called a success if nothing changes — the clinical pharmacologist and second endocrinologist named different informal intervals (one to two years versus indefinite monitoring with no fixed endpoint), left open for Wilhelmina's own input at her next visit.