Can You Transition from Prolia® (Denosumab) to Hormone Replacement Therapy (HRT)?
- purity carr
- Aug 5, 2024
- 6 min read
Updated: Aug 4
Understanding the Role of Oestrogen After Prolia
Introduction
One of the most common questions women ask is:
"Can I stop Prolia and simply continue on hormone replacement therapy (HRT) instead?"
The answer is generally no.
While oestrogen is one of the body's most important natural bone-protecting hormones and is highly effective at preventing postmenopausal bone loss, current evidence does not support using HRT alone as the follow-on treatment after stopping Prolia (denosumab).
This is because Prolia behaves differently from other osteoporosis medications. When it is stopped, bone turnover can rebound rapidly, causing sudden bone loss and an increased risk of multiple spinal fractures unless another potent antiresorptive medication is started.
This leaflet explains why this happens and what current evidence recommends.
How does Prolia work?
Bone is constantly being broken down by cells called osteoclasts and rebuilt by cells called osteoblasts.
Prolia works by blocking a protein called RANK ligand (RANKL), which is essential for osteoclast activity. This dramatically reduces bone breakdown, allowing bone density to increase over time.
Prolia is given as a 60 mg injection every six months.
It is an excellent treatment for osteoporosis and significantly reduces the risk of:
Spinal fractures
Hip fractures
Other osteoporotic fractures
Why is stopping Prolia different?
Unlike bisphosphonates, Prolia does not remain stored in the skeleton.
Its effect gradually wears off over approximately six months.
If another antiresorptive medication is not started when Prolia wears off, bone turnover can increase rapidly above pre-treatment levels. This is known as rebound bone turnover.
Research has shown that after stopping Prolia:
Bone turnover increases rapidly.
Bone density can fall quickly.
Multiple spinal (vertebral) fractures may occur.
Fractures can develop within months of the missed injection.
For this reason, Prolia should never be stopped without discussing a follow-on treatment plan with your healthcare professional.
Isn't oestrogen good for bones?
Yes.
Oestrogen is one of the body's most important natural bone-protecting hormones.
Before menopause, oestrogen helps keep bone breakdown and bone formation in balance. As menopause approaches and oestrogen levels fall, bone loss accelerates, particularly during the first five to ten years after the final menstrual period.
Hormone replacement therapy (HRT) helps by:
Reducing bone resorption.
Maintaining or increasing bone mineral density.
Reducing the risk of osteoporotic fractures.
Improving menopausal symptoms such as hot flushes, night sweats and vaginal dryness.
For women who are within 10 years of menopause or under 60 years of age, HRT is considered one of the most effective treatments for both menopausal symptoms and the prevention of osteoporosis, provided there are no contraindications.
A standard dose of transdermal oestradiol equivalent to approximately 50 micrograms per 24 hours (for example, a 50 microgram patch or an equivalent gel dose) has been shown to effectively prevent postmenopausal bone loss. Lower doses also provide bone protection, although the effect may be smaller.
Why isn't HRT enough after stopping Prolia?
Although HRT reduces bone resorption and is an excellent treatment for preventing postmenopausal bone loss, current evidence suggests that HRT alone does not adequately suppress the rebound increase in bone turnover that occurs after stopping Prolia.
For this reason, current osteoporosis guidelines do not recommend transitioning directly from Prolia to HRT alone.
In other words:
Prolia → HRT alone
is not considered a safe or evidence-based sequence because it may leave women at risk of rebound bone loss and vertebral fractures.
What is the recommended approach if Prolia needs to be stopped?
If you and your doctor decide that Prolia should be discontinued, another antiresorptive medication should be started to reduce the rebound effect.
For many women this will be an oral bisphosphonate, such as:
Alendronate 70 mg once weekly
Risedronate 35 mg once weekly
Risedronate 150 mg once monthly
If tablets are unsuitable or not tolerated, your doctor may recommend an intravenous bisphosphonate, most commonly zoledronic acid (Aclasta®).
When should the bisphosphonate be started?
The bisphosphonate is not routinely started while Prolia is still active, provided your injections are being given on time.
Instead, it is used to replace your next scheduled Prolia injection if the decision has been made to stop treatment.
This means:
Receive your final Prolia injection.
Count forward 6 months from that injection.
When your next Prolia injection would normally be due, start the bisphosphonate instead of receiving another Prolia injection.
Treatment should ideally begin at 6 months and no later than 7 months after the last Prolia injection.
Delaying treatment beyond seven months increases the risk of rebound bone loss and vertebral fractures.
How long will I need the bisphosphonate?
There is no single duration that is right for everyone.
Most women continue treatment for at least 12 months, and many require 18–24 months.
Some women, particularly those at very high fracture risk or who have received Prolia for many years, may require longer treatment.
The duration depends on:
Your fracture risk.
How long you received Prolia.
Your bone density (DEXA) results.
Your response to treatment.
Occasionally, bone turnover blood tests (such as CTX).
Your healthcare professional will advise what is appropriate for you.
Can I continue HRT while taking Prolia?
Yes.
Many women take HRT and Prolia together.
The two medications work in different ways and may complement one another when clinically appropriate.
HRT continues to provide:
Relief of menopausal symptoms.
Ongoing bone protection.
Preservation of muscle mass.
Improvement in urogenital symptoms.
Possible cardiovascular benefits when started in appropriately selected women early after menopause.
If you are benefiting from HRT, you do not usually need to stop it simply because you require Prolia.
Can HRT be added after the bisphosphonate?
Yes.
Once the skeleton has been stabilised following Prolia discontinuation, HRT may continue or be commenced in appropriate women for:
Menopausal symptom relief.
Additional bone protection.
Maintenance of muscle strength.
Long-term health benefits where appropriate.
However, HRT should not replace the recommended sequential bisphosphonate therapy immediately after stopping Prolia.
Lifestyle measures remain important
Medication works best alongside healthy lifestyle choices.
Aim to:
Maintain adequate calcium intake.
Correct vitamin D deficiency.
Perform regular weight-bearing exercise.
Include resistance training at least twice each week.
Avoid smoking.
Limit excessive alcohol intake.
Reduce falls risk through balance and strength training.
Dr Purity's Clinical Perspective
One of the most common misconceptions I encounter is that because HRT is excellent for bone health, it can simply replace Prolia when treatment is stopped. Unfortunately, current evidence suggests this is not the case.
HRT is one of the best treatments we have for preventing postmenopausal bone loss and remains an important part of osteoporosis prevention in appropriate women. However, the rebound increase in bone turnover after stopping Prolia is unique and much more dramatic than the gradual bone loss seen after menopause. For this reason, HRT alone has not been shown to provide sufficient protection during this transition.
The safest approach is to plan ahead. If Prolia is being discontinued, another antiresorptive medication, usually an oral bisphosphonate or intravenous zoledronic acid, should replace the next scheduled Prolia injection. Once your bones have been stabilised, HRT can continue to provide ongoing bone protection and menopause symptom relief if it remains appropriate for you.
Dr Purity's Key Messages
HRT is one of the most effective treatments for preventing postmenopausal bone loss.
A standard 50 microgram transdermal oestradiol patch (or equivalent gel dose) provides effective bone protection for many women.
Current evidence does not support replacing Prolia with HRT alone.
If Prolia is stopped, another antiresorptive medication should replace your next scheduled injection.
Oral bisphosphonates or intravenous zoledronic acid are the recommended follow-on treatments.
Many women continue HRT while receiving Prolia.
The duration of follow-on therapy should be individualised according to your fracture risk and response to treatment.
References
Healthy Bones Australia. Position Statement on Osteoporosis Management.
International Osteoporosis Foundation. Denosumab Discontinuation and Sequential Therapy Guidance.
Endocrine Society. Pharmacological Management of Osteoporosis in Postmenopausal Women: Clinical Practice Guideline.
Tsourdi E, Zillikens MC, Meier C, et al. Fracture risk and management after denosumab discontinuation. Osteoporosis International. 2021.
Cummings SR, Ferrari S, Eastell R, et al. Vertebral fractures after discontinuation of denosumab. Journal of Bone and Mineral Research. 2018.
The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2022.
International Menopause Society. Recommendations on Menopausal Hormone Therapy and Bone Health.
Therapeutic Guidelines Australia. Osteoporosis.
Important Information
This leaflet provides general educational information only and should not replace personalised medical advice. Decisions about continuing or stopping Prolia, commencing HRT, or transitioning to another osteoporosis medication should always be made in consultation with your healthcare professional. Treatment should be individualised according to your fracture risk, menopausal symptoms, bone density, medical history and personal preferences.
Purity Health Menopause & Wellbeing CentreDr Purity Carr | GP | Menopause Doctor“Personalised, evidence-based care.”
Author:📘 No. 1 Best seller - Low Histamine Living – Available on Kindle📗 Stop Smoking in 5 Days – Available on Amazon
Founder:10:10 Metabolic ResetMenopause Momentum Network
Weight Management and Metabolic Reset Skool: https://www.skool.com/menopause-momentum-network-3083/about
Comments