Zoledronic acid
bisphosphonate · osteoporosis
Third-party optionBy the Layer Nutrition editorial team
What this medicine is for
Zoledronic acid is a medicine in the “bisphosphonate (osteoporosis)” category. This medicine strengthens the bone and reduces the risk of fracture.
Pour Acide zolédronique en pratique : Renforce l'os et réduit le risque de fracture. On le prend en général sur la durée, dans le cadre d'un suivi régulier, et on ne l'interrompt pas de sa propre initiative.
Under which brands it is found
Zoledronic acid is used in about 8 presentations listed in France. It comes under various commercial names and as generics.
- Acide Zoledronique Altan
- Acide Zoledronique Biogaran
- Acide Zoledronique Mylan
- Acide Zoledronique Sandoz
- Acide Zoledronique Tillomed
- Acide Zoledronique Viatris
- Aclasta
- Zometa
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 zoledronic acid, bone rebuilds better when it has its two basic materials: calcium and vitamin D. Intakes must stay regular, and food is the first way to keep them up day after day.
Calcium is found mainly in dairy products such as milk, cheese and yoghurt, in leafy green vegetables such as kale, in fish whose bones are eaten such as sardines, and in fortified foods. The calcium in spinach is an exception: it is poorly absorbed by the body, which makes it an unreliable source despite its content.
Vitamin D helps regulate the calcium and phosphate that bone needs. It comes from oily fish such as salmon, sardines, herring and mackerel, but also from red meat, liver, egg yolks and fortified foods. Bringing these two groups together across your meals covers a good part of your needs, in addition to your treatment.
How zoledronic acid works
Zoledronic acid belongs to the bisphosphonate family. Its target in bone is the osteoclast, the cell responsible for breaking down old bone tissue. Inside this cell, it blocks a specific enzyme, farnesyl pyrophosphate synthase, which belongs to the mevalonate pathway. This enzyme makes molecules that the osteoclast needs to survive and to work.
By blocking this enzyme, the drug prevents the prenylation of small GTPase proteins that the osteoclast needs to function. Deprived of these proteins, the cell can no longer break down mineralised bone and eventually undergoes apoptosis, its programmed death. Bone resorption slows, bone loss reverses and the skeleton becomes stronger.
Why this treatment is prescribed
Zoledronic acid is indicated for the treatment and prevention of osteoporosis in postmenopausal women, to increase bone mass in men, in osteoporosis caused by corticosteroids and in Paget's disease of bone. What these situations have in common is bone that breaks down faster than it rebuilds, which leaves it prone to fractures.
Its benefit was established by the HORIZON trial (Black et al., New England Journal of Medicine, 2007). In postmenopausal women with osteoporosis, a yearly 5 mg infusion reduces the risk of vertebral fractures by 70 percent and the risk of hip fractures by 41 percent over 3 years compared with placebo, with hip events falling from 2.5 to 1.4 percent.
How the treatment unfolds
Zoledronic acid is given as a 5 mg intravenous infusion, over at least 15 minutes, in a care setting. The schedule is one infusion per year to treat osteoporosis and one infusion every 2 years for prevention. Because it is given intravenously, the dose does not depend on meals or on a daily timing.
A single injection acts for a long time. Clearance from the blood occurs in three phases, with a terminal half-life of 146 hours, and 39 percent of the dose leaves unchanged in the urine within 24 hours. The rest binds to bone and is then released very slowly into the circulation, which explains the long duration of action and the spacing between infusions. The yearly schedule maintains this bone saturation from one infusion to the next.
The effects to know about
The most common effect is a so-called acute phase reaction, which occurs in the days after the infusion and resembles a passing flu-like state: fever, joint and muscle pain, headache. It eases within a few days and lessens with later infusions. Over the whole 3-year follow-up, the adverse effects most often reported in the osteoporosis trial were arthralgia in 23.8 percent of patients, fever in 17.9 percent, headache in 12.4 percent, myalgia in 11.7 percent and a flu-like syndrome in 8.8 percent.
A marked drop in blood calcium, below 7.5 mg/dL, affected about 0.2 percent of patients, with no symptomatic form observed, which is why any hypocalcaemia should be corrected before the first infusion. Two rare but serious effects have been reported with bisphosphonates, including zoledronic acid: osteonecrosis of the jaw and atypical, low-energy femoral fractures. Thigh or groin pain should prompt an assessment for an incomplete femoral fracture.
Calcium and vitamin D, the foundations of bone
The drug curbs the destruction of bone, but rebuilding calls for raw material. Supplementation is required during treatment: at least 1200 mg of calcium and 800 to 1000 IU of vitamin D per day in osteoporosis. Without these intakes, the benefit for bone strength cannot be fully expressed.
This foundation must be in place even before the first infusion. Hypocalcaemia and vitamin D deficiency must be corrected effectively before starting treatment, because zoledronic acid tends to lower blood calcium. Food is the simplest and most lasting way to maintain these reserves, alongside what the doctor may prescribe.
Interactions and monitoring
Kidney function is checked before each infusion, through a serum creatinine measurement and a clearance calculation using the Cockcroft-Gault formula. The drug is contraindicated in cases of hypocalcaemia, creatinine clearance below 35 mL/min and acute kidney failure. This check determines the go-ahead for each yearly injection.
Some combinations call for caution. Other drugs that are toxic to the kidney, such as non-steroidal anti-inflammatory drugs, add to the renal risk. Loop diuretics increase the risk of hypocalcaemia, and aminoglycosides can prolong the lowering of blood calcium. Reporting all of one's treatments allows the doctor to adjust the laboratory monitoring.
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 most common side effects of zoledronic acid?
The package leaflet commonly reports a flu-like syndrome in the days following the infusion: fever, muscle or joint pain, fatigue, headache, most often after the first administration. These reactions are usually temporary. For your own situation, refer to the package leaflet and talk to your doctor or pharmacist.
How often is zoledronic acid given?
Zoledronic acid is given by intravenous infusion, on a schedule set by the prescriber according to the indication. The timing of the infusions is decided and monitored by your doctor. Refer to the package leaflet and to your doctor or pharmacist for any question about when the infusions take place and how far apart they are spaced.
Do you need a dental check-up before a zoledronic acid infusion?
The package leaflet notes a risk of osteonecrosis of the jaw and recommends, before treatment, a dental examination and any necessary dental care, reporting any dental problem. Mention it to your dentist and your doctor. Follow the package leaflet and the advice of your doctor or pharmacist.
Zoledronic acid and pregnancy or breastfeeding: what precautions?
The package leaflet states that zoledronic acid is not intended for women who are pregnant or breastfeeding. If you are pregnant, plan to become pregnant or are breastfeeding, tell your doctor before any infusion. Refer to the package leaflet and to the advice of your doctor or pharmacist.
Is zoledronic acid suitable if you have kidney problems or are elderly?
The package leaflet specifies that kidney function is taken into account and that good hydration is recommended around the time of the infusion, with added precautions in some people. The assessment is up to the prescriber. For your own case, rely on the package leaflet and on your doctor or pharmacist.
Why monitor calcium and vitamin D with zoledronic acid?
The public package leaflet for zoledronic acid recommends an adequate intake of calcium and vitamin D, because this treatment is associated with a risk of low blood calcium, to be monitored by your doctor. The active to consider on the nutrition side is calcium, as carbonate or citrate, and vitamin D as cholecalciferol (vitamin D3). Monitoring of blood calcium and vitamin D is up to your doctor, who adjusts intake to your situation.
Ces réponses portent sur le volet nutritionnel. Pour toute question sur votre médicament, la notice et votre médecin ou pharmacien font foi.