Denosumab
anti-RANKL antibody · osteoporosis
Third-party optionBy the Layer Nutrition editorial team · How the atlas classifies the 664 molecules
What this medicine is for
Denosumab is a medication in the "anti-RANKL antibody (osteoporosis)" category. This medication strengthens bone solidity and reduces the risk of fracture.
For Denosumab in practice: Strengthens bone and reduces the risk of fracture. Its conditions of use depend on the situation, within the framework set by the doctor.
Under which brands it is found
In France, about 16 reimbursable presentations containing Denosumab are recorded. It comes under various trade names and in generic form.
- Acvybra
- Bomyntra
- Conexxence
- Denbrayce
- Izamby
- Jubbonti
- Jubereq
- Kefdensis
- and other presentations
Original brand-name products and generics deliver the same active substance; the choice between them is made with your doctor or pharmacist.
On the plate: calcium and vitamin D
On denosumab, supplementation with calcium and vitamin D goes with the treatment as a matter of course. Food lays the groundwork, day after day, and remains the simplest lever to keep up.
Calcium builds and maintains bone. The NHS puts the need of an adult aged 19 to 64 at around 700 mg per day. It is found in dairy products such as milk, cheese and yoghurt, in green vegetables such as kale and okra, in fish with soft bones such as the sardine, and in fortified foods.
Vitamin D regulates the body's calcium and phosphate and keeps bones, teeth and muscles healthy. The NHS recommends 10 micrograms per day for adults. It comes mainly from oily fish such as salmon, sardine and mackerel, from egg yolks, red meat and fortified foods.
How denosumab works
Denosumab is a fully human monoclonal antibody of the IgG2 type. It binds to a protein called RANKL and prevents it from attaching to its receptor RANK, found on the surface of osteoclast precursors and mature osteoclasts. It is the osteoclasts that dig into and break down bone tissue. By blocking this signal, denosumab slows the formation, activity and survival of these cells, and thereby reduces bone resorption.
By slowing this demolition work, denosumab lets bone rebuilding gain the upper hand. Bone mineral density increases, and the risk of fracture goes down. In postmenopausal women at high risk, this reduction applies to vertebral fractures, non-vertebral fractures and hip fractures.
Why denosumab is prescribed
Denosumab, sold under the name Prolia in this indication, is used to treat osteoporosis in postmenopausal women and in men at increased risk of fracture. The aim is to strengthen a weakened skeleton and to prevent the fractures that seriously complicate daily life, in particular hip fracture.
It is also indicated for the bone loss caused by certain hormone-suppressing treatments. This is the case with androgen deprivation used in prostate cancer, and with the aromatase inhibitors used in breast cancer. These treatments speed up demineralisation, and denosumab helps protect the bone for the duration of their use.
How the treatment unfolds
In osteoporosis, the dose is 60 mg in a single subcutaneous injection every 6 months. The injection is given in the thigh, the abdomen or the upper arm. Unlike oral bisphosphonates, denosumab requires neither fasting nor any particular upright position, and no interaction with meals has been described.
After the injection, bioavailability is around 61 percent and the concentration reaches its peak around the tenth day. The mean half-life is estimated at between 25 and 32 days depending on the source. The six-month rhythm shapes the whole treatment: keeping to the date of the next injection matters, and stopping remains a decision to be made with the doctor, never alone.
The effects to know about and their frequency
In the FREEDOM trial, conducted in osteoporotic postmenopausal women against placebo, the most frequently reported effects were close to those of placebo: back pain 34.7 percent versus 34.6, pain in the extremities 11.7 versus 11.1, musculoskeletal pain 7.6 versus 7.5, hypercholesterolaemia 7.2 versus 6.1, cystitis 5.9 versus 5.8, and upper respiratory tract infection 4.9 versus 4.3.
The EMA classifies the effects of Prolia by frequency. Very common, meaning at least 1 case in 10, are pain in the extremities and musculoskeletal pain. Common, from 1 in 100 to 1 in 10, are constipation, rash, eczema and urinary tract infection. Rare, from 1 in 10,000 to 1 in 1,000, are hypocalcaemia, osteonecrosis of the jaw and atypical femoral fractures.
Calcium, a point to watch
The established nutritional impact of denosumab is hypocalcaemia: by slowing the release of calcium from bone, it can lower blood calcium. In osteoporosis, the EMA classifies this hypocalcaemia as rare, that is between 1 case in 10,000 and 1 in 1,000. Pre-existing hypocalcaemia must be corrected before starting, as it is a contraindication, and the risk of severe hypocalcaemia is increased in advanced chronic kidney failure.
Supplementation is planned for all patients: 1,000 mg of calcium per day and at least 400 IU of vitamin D per day for the duration of treatment. Food supports this intake day to day, in addition to your treatment, never in its place.
Interactions and monitoring
Some combinations call for caution. Denosumab should not be combined with etelcalcetide, because of a risk of severe hypocalcaemia. Corticosteroids and systemic immunosuppressants also call for vigilance, as they raise the risk of infection. Denosumab is moreover contraindicated during pregnancy and in cases of hypersensitivity: effective contraception is required during treatment and for at least 5 months after the last dose.
Laboratory monitoring rests above all on checking blood calcium, especially during the first weeks. StatPearls advises also monitoring creatinine, calcium, phosphorus and magnesium at the start of treatment, then checking vitamin D and calcium periodically. This monitoring makes sure that blood calcium stays within limits throughout the treatment.
Sources
Related molecules
To explore within the « Bones and joints » family and its neighbours.
See the entire « Bones and joints » family · Back to the atlas
Supplements to consider
Beyond the plate, a single isolated nutrient can be worth discussing, to confirm with your doctor or pharmacist. Here is which one and in which form.
Calcium
Calcium is the most abundant mineral in the body, involved in bone health. Calcium citrate is well absorbed, including away from meals, whereas carbonate requires an acidic environment for its absorption.
Preferred form calcium citrate (does not depend on gastric acidity)
Vitamin D3 (cholecalciferol)
Vitamin D is a fat-soluble vitamin. The D3 form (cholecalciferol) is the one adopted by most guidelines. It is better absorbed when taken during a meal that contains fats.
Preferred form D3 (cholecalciferol), during a fatty meal
Frequently asked questions
What are the side effects of denosumab?
Its patient leaflet notably lists pain in the limbs, musculoskeletal pain and a drop in blood calcium (hypocalcaemia). Effects vary from person to person: refer to your medication's leaflet and discuss any symptom with your doctor or pharmacist.
Why is blood calcium monitored while on denosumab?
Denosumab can lower the level of calcium in the blood, a risk that is higher with kidney impairment or vitamin D deficiency. That is why blood calcium is monitored around the injections. Report any tingling, spasms or muscle stiffness to your doctor or pharmacist without delay, and follow the leaflet's instructions.
What happens when you stop denosumab?
France's medicines agency (ANSM) and learned societies have warned of a rebound effect after stopping, with a risk of vertebral fractures that are sometimes multiple, especially if you have had a fracture before. Stopping is never a decision to make on your own: it is a conversation to have with your doctor, who arranges any follow-on treatment.
Is denosumab safe to take during pregnancy?
Its leaflet states that it should not be used during pregnancy. This question is for your doctor, who assesses your situation on a case-by-case basis. Do not change your treatment on your own: talk about it with your doctor or pharmacist.
Do you need calcium and vitamin D while taking denosumab?
Denosumab's summary of product characteristics (SmPC) recommends an adequate intake of calcium and vitamin D during treatment, except in cases of excess calcium. Research also links this intake to a better change in bone density. Monitoring your blood calcium and your actual needs are to be set with your doctor.
What form of calcium and vitamin D should you take?
For vitamin D, the reference form is cholecalciferol (vitamin D3). For calcium, the main forms are calcium carbonate and calcium citrate, the latter often being better tolerated by the digestive system. The form, and whether a supplement is appropriate, depend on your test results: it is a decision to make with your doctor or pharmacist.
Ces réponses portent sur le volet nutritionnel. Pour toute question sur votre médicament, la notice et votre médecin ou pharmacien font foi.