A quick note from me, I am not a prescriber, I am writing from my point of view. Do not stop any medications without consulting with your doctor first.
After denosumab was discontinued, the rate of new vertebral fractures rose from 1.2% on treatment to 7.1% per year afterwards. After stopping the medication women were 61% more likely to fracture multiple vertebrae compared to 39% of women coming off the placebo.
That’s from post hoc analyses of the FREEDOM and FREEDOM Extension trials, published in the Journal of Bone and Mineral Research in 2022. This research covered postmenopausal women with osteoporosis, which is the vast majority of you reading this.
Denosumab works by switching off the cells that resorb bone. It doesn’t change them permanently, it blocks them whilst active. However, when you stop the drug and the suppression lifts, it lifts quickly. Bone turnover overshoots for around 6-18 months after the last dose.
Which is why the six-monthly injection is not a flexible appointment. It’s not “I’ll pick it up after the holiday.” Not a “the surgery didn’t ring me so I assumed it was fine.”
If you have missed a denosumab dose, stop reading this and ring your prescriber. That’s not a training problem and I can’t help you with it.
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Most drugs prescribed for bone fall into one of three groups, and they all affect bone differently.
Antiresorptives:
Bisphosphonates (alendronate, risedronate, zoledronate) and denosumab.
These slow demolition and resorption. Your skeleton is constantly being taken apart and rebuilt (this is normal). Antiresorptives slow the taking-apart, which lets the rebuilding catch up leading to bone density rises.
Bisphosphonates bind into the bone mineral itself and keep working for a long time after the last dose. In comparison to Denosumab which is a circulating antibody with nothing left behind. Same job, with a rapid exit after the last dose.
Anabolics:
Teriparatide, abaloparatide, romosozumab.
These stimulate new bone formation, rather than slowing loss. They’re reserved for high-risk cases, because they’re expensive, and they’re time-limited.
Romosozumab sits slightly apart because it does both. It stimulates formation and suppresses resorption for its first several months.
Hormone therapy.
Oestrogen
Is the reason most of this is happening in the first place. And it has such a huge effect on women, I only touch it through the bone lens. But briefly, it preserves bone, and it stops preserving bone when you stop taking it.
The DATA-Switch study (Leder et al., Lancet 2015) took 94 postmenopausal women and gave them two years of teriparatide followed by two years of denosumab, or the same two drugs the other way round.
Same drugs and duration but in a different order caused significantly different results.
Teriparatide first, then denosumab, bone density kept climbing throughout.
Denosumab first, then teriparatide, bone density fell. Follow-up imaging showed deterioration in cortical bone at the shin and forearm (not the spine and hip which we would normally look for).
The reason is mechanical, in a sense. An anabolic drug works by revving up bone remodelling. If you’ve just spent two years suppressing remodeling with an antiresorptive, the anabolic drug wakes up the demolition crew before the building crew gets organised, and you lose ground before you gain it.
Build first and then protect what you built. Not the other way round.
The ARCH trial points the same direction. In 4,093 postmenopausal women with osteoporosis and an existing fragility fracture, twelve months of romosozumab followed by alendronate produced a 48% lower risk of new vertebral fracture over 24 months than alendronate alone.
If you are high risk and your consultant is considering an anabolic, the order of the conversation is not a detail. It is worth knowing that anabolic-first has the best evidence behind it, and worth asking about if nobody has raised it.
Frustratingly for me as a physiotherapist who writes about bone health, I would love to tell you that we get massive boosts to bone density with weight training on top of the medication.
Free posts tell you what the evidence says. Paid posts tell you what to do on Monday morning.
This week, paid members get the detailed breakdown of when to and what to do. If you want your next DEXA to move, that’s the part that moves it.
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