Bisphosphonates work by binding to the surface of bone and slowing the activity of osteoclasts - the cells that break down old bone tissue. By reducing bone resorption, they shift the balance of bone remodelling in favour of the bone-building side, allowing density to stabilise and in many women modestly improve over time.

They do not add new bone in the way anabolic medications do but for most women with osteoporosis or high-risk osteopenia, they are effective, well-tolerated, and widely available.

CALLOUT: Bisphosphonates have been used for over 30 years and are among the most studied medications in medicine. The evidence base behind them for both efficacy and safety is substantial.

The three main bisphosphonates

  • Alendronate (Fosamax) is taken daily or once weekly as an oral tablet. The most commonly prescribed bisphosphonate globally
  • Risedronate (Actonel) is taken daily, once weekly, or once monthly. Often better tolerated than alendronate for women with digestive sensitivity
  • Zoledronic acid (Reclast/Aclasta) is given as a 15-minute intravenous infusion once a year at a clinic or hospital. The most potent bisphosphonate and the most convenient for women who struggle with daily or weekly oral medication

CALLOUT: The choice between oral and infusion bisphosphonates is often about lifestyle fit as much as clinical preference. A woman who travels frequently, has an unpredictable morning routine, or has a history of digestive problems may do better on an annual infusion than a weekly tablet.

The dosing rules that matter

For oral bisphosphonates, the dosing requirements are strict and for good reason. The medication needs to reach the stomach intact and be absorbed efficiently. If taken incorrectly, it can cause oesophageal irritation or simply not be absorbed properly.

  • Take first thing in the morning, before any food, drink, or other medications
  • Swallow with a full glass of plain water, not coffee, juice, or mineral water
  • Stay upright sitting or standing for at least 30 minutes afterwards
  • Do not eat or take other medications during this window

QUOTE: "The 30-minute rule is not optional. It is what protects your oesophagus and ensures the medication is absorbed. Building it into a morning routine using Lenari’s reminders makes it manageable."

What to expect in the first weeks

Some women experience digestive side effects when starting an oral bisphosphonate, such as heartburn, nausea, or stomach discomfort. These often settle within the first few weeks as your body adjusts. Taking the medication exactly as directed, with a full glass of water, minimises the risk.

For zoledronic acid, the most common reaction is a flu-like response in the 24 to 72 hours after the infusion - fever, muscle aches, fatigue, and headache. This is an immune response to the medication, not an allergic reaction, and it typically resolves on its own. It is more common after the first infusion and often less pronounced with subsequent annual doses. Paracetamol can help manage symptoms.

The rare side effects worth knowing about

Two rare but well-publicised side effects deserve a clear explanation because they cause disproportionate anxiety when encountered out of context.

Osteonecrosis of the Jaw (ONJ) is a condition in which bone in the jaw fails to heal properly, typically following a dental procedure. At osteoporosis doses, the risk is low - much lower than the figures you may have read online, which largely come from cancer treatment data where doses are far higher.

CALLOUT: Keep your doctor and dentist informed that you are on a bisphosphonate, and maintain good dental hygiene. Our article on side effects in this section covers ONJ in full, including what the latest guidelines say about dental procedures and whether stopping your medication beforehand is ever necessary.

Atypical femoral fractures are stress fractures of the thigh bone that occur in a small number of patients on long-term bisphosphonate therapy, typically after five or more years of use. They are rare, and the absolute risk is low compared to the fractures the medication prevents. Thigh or groin pain during bisphosphonate treatment should be reported to your doctor.

CALLOUT: These rare side effects are real and you deserve to know about them. But context matters. The fractures bisphosphonates prevent, hip fractures especially, carry far greater consequences than the rare complications associated with the medication itself.

How long do bisphosphonates stay in the body?

Bisphosphonates bind to bone and remain there for years after you stop taking them. This means their protective effect does not disappear immediately if treatment is paused. This is the rationale behind "bisphosphonate holidays" - planned breaks from oral bisphosphonates after several years of use, to reduce the small cumulative risk of atypical femoral fractures while retaining some ongoing protection.

Whether a bisphosphonate holiday is appropriate for you, and when, is a decision your doctor will make based on your individual fracture risk, your scan results, and how long you have been on treatment.

CALLOUT: Taking alendronate, risedronate, or zoledronic acid or considering one? Open the medication explainer for the one that's relevant to you. [Go to medication guide →]