What is risedronate used for. How does risedronate work to treat osteoporosis. Who can take risedronate and when is it not suitable. How to properly take risedronate tablets. What are the potential side effects of risedronate. How is risedronate treatment monitored. What are the long-term considerations for risedronate use.

Understanding Risedronate: An Effective Osteoporosis Medication

Risedronate, also known as risedronic acid, is a medication classified as a bisphosphonate. It plays a crucial role in the treatment of osteoporosis, a condition characterized by weakened bones that are more susceptible to fractures. Bisphosphonates like risedronate are the most commonly prescribed treatments for osteoporosis due to their effectiveness in strengthening bones and reducing fracture risk.

While risedronate may be offered as a first-line treatment for osteoporosis, it is more frequently used as a second-line option when patients need to switch from their initial medication. This versatility makes risedronate an important tool in the management of osteoporosis for many individuals.

How does risedronate work to combat osteoporosis?

Risedronate functions by targeting the natural bone remodeling process. In healthy bones, there is a constant cycle of breakdown and rebuilding performed by specialized cells. Osteoporosis occurs when this balance is disrupted, resulting in more bone being broken down than rebuilt. Risedronate intervenes in this process by:

• Slowing down the activity of cells responsible for breaking down bone tissue
• Helping to restore the balance between bone breakdown and formation
• Increasing overall bone density and strength

By restoring this balance, risedronate helps make bones stronger and reduces the risk of fractures, particularly in areas such as the hip and spine. It’s important to note that while risedronate significantly decreases fracture risk, it cannot eliminate the possibility entirely. Additionally, risedronate is not a pain reliever and won’t directly address pain from existing fractures.

Who Can Benefit from Risedronate Treatment?

Risedronate is primarily prescribed for individuals with osteoporosis or those at high risk of bone fractures. The medication is approved for use in both postmenopausal women and men. In some cases, doctors may prescribe risedronate to younger women, although this is less common.

Often, patients are initially prescribed alendronate, another bisphosphonate with similar effects. However, risedronate may be recommended as an alternative, especially for those with sensitive digestive systems. This is because some individuals find risedronate to be gentler on the stomach and esophagus compared to alendronate.

When might risedronate be unsuitable?

Despite its benefits, risedronate is not appropriate for everyone. Conditions that may preclude its use include:

• Difficulty swallowing tablets
• Esophageal disorders, such as Barrett’s esophagus
• Inability to remain upright for at least 30 minutes after taking the medication
• Severe kidney problems
• Low blood calcium levels (hypocalcemia)
• Pregnancy or breastfeeding

If you have any of these conditions, your healthcare provider will likely explore alternative treatments for osteoporosis.

Proper Administration of Risedronate: Dosage and Instructions

Risedronate is available in two main dosage forms:

1. A 5mg tablet taken daily
2. A 35mg tablet taken weekly

Adhering to the correct administration protocol is crucial for maximizing the effectiveness of risedronate and minimizing potential side effects. Here are the key steps to follow:

For weekly tablets:

• Take the tablet on the same day each week
• Swallow the tablet whole with a full glass of plain tap water first thing in the morning
• Wait at least 30 minutes before consuming any food, drink (other than water), or other medications
• Remain upright (sitting or standing) for at least 30 minutes after taking the tablet

For daily tablets:

• Follow the same instructions as for weekly tablets
• If morning administration is not possible, ensure you take the tablet on an empty stomach, at least 2 hours before or after eating or drinking anything other than plain water

Is it necessary to avoid other medications when taking risedronate? Yes, it’s important to wait at least 30 minutes (some doctors recommend up to 4 hours) before taking other medications or supplements, especially calcium supplements, as they can interfere with risedronate absorption.

Monitoring and Managing Risedronate Treatment

When starting risedronate treatment, regular monitoring is essential to ensure its effectiveness and address any potential issues. Typically, patients will have follow-up appointments after approximately three months and again after one year of treatment.

During these check-ups, healthcare providers will assess:

• Proper medication adherence
• Any side effects or complications
• Overall treatment efficacy

It’s crucial to communicate any concerns or side effects to your healthcare provider during these appointments. They may adjust your treatment plan if necessary.

How long should risedronate treatment continue?

The duration of risedronate treatment varies depending on individual circumstances. While some patients may benefit from long-term use, others may be advised to take a “drug holiday” after several years of treatment. This decision is based on factors such as:

• Bone density improvements
• Fracture risk
• Overall health status
• Potential long-term side effects

Your healthcare provider will regularly assess the need to continue or modify your treatment plan.

Potential Side Effects and Precautions with Risedronate Use

While risedronate is generally well-tolerated, like all medications, it can cause side effects in some individuals. Common side effects may include:

• Stomach upset or nausea
• Heartburn or acid reflux
• Muscle or joint pain
• Headache

More serious but rare side effects can include:

• Esophageal irritation or ulceration
• Osteonecrosis of the jaw (ONJ)
• Atypical femur fractures

Can the risk of side effects be minimized? Yes, following the proper administration instructions, such as taking the medication with a full glass of water and remaining upright afterward, can significantly reduce the risk of digestive side effects.

Special precautions and considerations

Certain situations require extra caution when using risedronate:

• Dental procedures: Inform your dentist about risedronate use, as it may affect healing after dental work
• Pregnancy and breastfeeding: Risedronate is not recommended during these periods
• Kidney function: Dose adjustments may be necessary for individuals with impaired kidney function

Complementary Measures to Enhance Risedronate Effectiveness

While risedronate is a powerful tool in managing osteoporosis, combining it with other bone-healthy practices can optimize its benefits. Consider incorporating the following measures:

• Adequate calcium and vitamin D intake
• Regular weight-bearing and resistance exercises
• Smoking cessation
• Limiting alcohol consumption
• Fall prevention strategies

How do these measures complement risedronate treatment? These lifestyle modifications work synergistically with risedronate to improve bone health, reduce fracture risk, and enhance overall well-being.

Risedronate vs. Other Osteoporosis Treatments: A Comparative Overview

Risedronate is one of several treatment options available for osteoporosis. Understanding how it compares to other medications can help patients and healthcare providers make informed decisions about treatment plans.

Risedronate vs. Alendronate

Both risedronate and alendronate are bisphosphonates, but they have some differences:

• Alendronate is often prescribed as a first-line treatment
• Risedronate may be gentler on the digestive system for some patients
• Dosing schedules may differ (weekly or daily for risedronate, weekly or monthly for alendronate)

Risedronate vs. Denosumab

Denosumab is a different class of osteoporosis medication:

• Administered as an injection every six months
• May be preferred for patients with kidney problems
• Can have a more rapid onset of action compared to bisphosphonates

Risedronate vs. Hormone Therapy

Hormone therapy (estrogen or estrogen with progestin) was once commonly used for osteoporosis prevention:

• Can address other menopausal symptoms
• Associated with certain health risks, making it less commonly used for osteoporosis alone
• Risedronate focuses specifically on bone health without systemic hormonal effects

How does a healthcare provider determine the best treatment option? The choice depends on factors such as the patient’s overall health, fracture risk, medication history, and personal preferences. Your doctor will work with you to select the most appropriate treatment plan.

Future Developments and Research in Osteoporosis Treatment

As medical research advances, new treatments and improvements to existing therapies like risedronate are continually being explored. Some areas of ongoing research include:

• Development of new bisphosphonate formulations with improved absorption or fewer side effects
• Investigation of combination therapies to enhance treatment efficacy
• Exploration of novel drug targets to address different aspects of bone metabolism
• Personalized medicine approaches to tailor osteoporosis treatments to individual patient profiles

How might these developments impact future osteoporosis treatment? As research progresses, patients may benefit from more effective, personalized, and convenient treatment options, potentially improving outcomes and quality of life for those with osteoporosis.

In conclusion, risedronate remains a valuable tool in the management of osteoporosis, offering significant benefits in terms of bone strength and fracture prevention. By understanding its proper use, potential side effects, and how it fits into the broader landscape of osteoporosis treatment, patients and healthcare providers can make informed decisions to optimize bone health and overall well-being. As with any medical treatment, regular communication with your healthcare team is essential to ensure the best possible outcomes and to address any concerns that may arise during the course of treatment.

Risedronate (risedronic acid) – drug treatment for osteoporosis

Risedronate is a type of medication called a bisphosphonate. Bisphosphonates are the most common treatments for osteoporosis. You may be offered risedronate as a first treatment for osteoporosis. But it’s more likely to be used as a second treatment, if you’ve been advised to change to a different drug for any reason. 

What does risedronate do and how does it work?

Risedronate can help to make your bones stronger and reduce your risk of broken bones, including hip and spinal fractures. 

Bones are made up of living tissue. The inside of our bones is constantly being broken down and rebuilt by specialist bone cells. As long as this process is in balance, your bones should stay healthy and strong. 

But if the process becomes out of balance, our bodies can start to break down more bone than we build. This can cause the bones to become weaker and more likely to break easily. 

Risedronate works by slowing down the cells that break down bone. This helps to restore the balance and make your bones stronger. 

You may still break a bone while taking risedronate. If this happens, it doesn’t necessarily mean the drug isn’t working. No medication can stop all fractures, but taking risedronate will make them much less likely. 

Risedronate is not a pain-relieving medicine, so it won’t reduce the pain caused by broken bones. But there are other treatments and ways to manage pain. 

Who can have risedronate?

Risedronate may be suitable if you have osteoporosis, or if your risk of breaking a bone is high enough to need a drug treatment. 

It is licensed for use in women who have been through the menopause, and for men. Doctors will occasionally offer risedronate to younger women. 

People are usually offered a very similar tablet, called alendronate, to start with. But you may be offered risedronate instead, particularly if you have a sensitive stomach or food pipe. This is because some people may find it gentler on the digestive system than alendronate.  

Risedronate can also be used as a second drug treatment. For example, you might swap risedronate if you’re having problems with your first treatment, or if you’ve been on your first drug for several years and your doctor has recommended a change. 

When is risedronate not suitable?

Risedronate may not be suitable if you:

• can’t swallow tablets 
• have a problem with your oesophagus (gullet or food pipe), such as Barrett’s oesophagus 
• can’t stand or sit up for at least half an hour (see below) 
• have severe kidney problems 
• have a low blood calcium level (hypocalcaemia) – you’ll need to increase your intake of calcium and vitamin D before you can start risedronate 
• are pregnant or breast-feeding. 

How do I take risedronate?

Risedronate is available as either: 

• 1 tablet (5mg) every day 
• 1 tablet (35mg) every week. 

The following steps are important for ensuring the treatment works properly. They will also help to make side effects less likely (see below). 

Weekly tablets 

Make sure you take your tablets regularly and correctly, on the same day each week. You may want to make a note in your diary or set a reminder on your phone, to help you remember. 

Take your tablet as soon as you wake in the morning 

It’s very important to take risedronate on an empty stomach, as soon as you wake up. Swallow the tablet whole, with a glass of plain tap water. It’s important not to crush, chew or suck it. 

Then wait at least 30 minutes before having your first food or drink of the day (other than plain tap water). This is to make sure your body can absorb and use the drug. 

If you forget to take your weekly tablet, wait until the next morning before taking it. Then return to your usual day the following week. 

Don’t take other medications or supplements during this time

If you take calcium supplements, wait at least half an hour after taking risedronate. This is because calcium can affect how well the drug is absorbed. Some doctors suggest waiting up to four hours, to leave even more time for the drug to be absorbed. 

Stay upright for at least 30 minutes afterwards 

You must not lie down for at least half an hour after taking your tablet. This helps the tablet go down quickly into the stomach where it is absorbed. Your food pipe is more likely to become irritated if you lie down straightaway.

Daily tablets 

Follow the instructions above. But if you’re on the daily dose and can’t take your tablet in the morning, you can take it later in the day – as long as you don’t eat or drink anything (other than plain tap water) for two hours before or after taking the tablet. 

How will my treatment be monitored? 

When you start on risedronate, you may have an appointment after around three months, and again after one year. This is to check you’re taking your treatment properly and not having any problems. Tell the doctor, nurse or pharmacist if you have any side effects (see below). They may be able to suggest ways to help manage them. 

If you break a bone while taking risedronate, speak to your GP. Breaking a bone doesn’t necessarily mean your treatment isn’t working. But it may be a good idea to have a bone health assessment. 

After about five years on risedronate, you should have a formal treatment review. Ask your doctor when this should happen if you’re unsure. 

At this review, your doctor will check if you still need a drug treatment, and that risedronate is still the right treatment for you. 

You may have a bone density scan as part of your review, which will give your doctor some information about your bone strength. But they will need to consider other things as well, such as whether you’ve broken any bones since starting on risedronate. 

While there’s no clear way to prove for certain that your treatment is working, research has shown that osteoporosis drug treatments like risedronate are effective at lowering the risk of broken bones.  

Following your review, your doctor may advise you to: 

• stay on risedronate for another five years 
• stop treatment for a year or two, if this is safe for you – this is known as a treatment pause 
• start a different drug treatment instead of risedronate 
• stop having any treatment. 

Risedronate is a long-lasting treatment and should keep helping your bones for about 1-2 years after you stop taking it. Your doctor can advise you on what’s best for you, based on your own situation. 

What are the possible side effects? 

As with any drug, risedronate can sometimes cause side effects. The most common side effects are listed below, along with some rare problems that might very occasionally happen after several years of treatment. 

It is important to remember that in general, side effects are less common than many people think. Most people on risedronate don’t have any problems. Even if you do get side effects at first, they usually improve quickly and there are ways to manage them.  

For a full list of possible side effects, look at the patient information leaflet that comes with your treatment. If you don’t have a copy, ask your doctor or pharmacist for one. 

It’s important to understand that many of these problems aren’t actually caused by the drug. When a medicine is first tested, the people taking it have to report anything unusual to the researchers. The problems they report are often just as common in people who aren’t taking the drug. 

The following table has information on the main side effects and how common they are. For example, fewer than 1 person in every 10 people who take risedronate will get problems with their oesophagus (food pipe) or heartburn. The other 9 in every 10 people who use the drug will not have this problem. 

Side effect	How common is it?	What can I do about it?
Inflamed oesophagus (food pipe), sore throat, difficulty swallowing. A painful, burning feeling in your chest (heartburn)	Less than 1 in 10	Take the tablet with a full glass of tap water. Stay upright and avoid bending forward for at least 30 minutes afterwards. This should stop the tablet from sticking in your food pipe. If the problem doesn’t improve, tell your doctor.
Bone, joint or muscle pain	Less than 1 in 10	This usually improves as your body gets used to the new medicine. A simple pain-relieving medication, such as paracetamol, may help.
Headache	Less than 1 in 50	A simple pain-relieving medication, such as paracetamol, should help.
Eye inflammation, causing pain or blurred vision	Less than 1 in 100	Tell your doctor if you already have an inflammatory eye condition or develop symptoms such as a painful red eye.

Rare health risks:

Atypical (unusual) thigh bone fracture	Less than 1 in 1,000	This is a rare type of thigh bone fracture that can occasionally happen after many years of treatment, even with little or no force.
Osteonecrosis of the jaw	Less than 1 in 1,000	This is an extremely rare problem where healing inside the mouth is delayed, usually after major dental treatment. The general advice is to maintain good oral hygiene and have regular dental check-ups.

If you do get any side effects that don’t go away, it may help to: 

• make sure the problem isn’t caused by any other medication you are taking
• tell your doctor or pharmacist, who may be able to help find out what is causing the problem
• ask your doctor or pharmacist about other treatments that may suit you better. 

Making a decision about treatment 

As with any treatment, there are advantages and disadvantages to using risedronate. You should think about these when deciding whether to have risedronate, and about what’s important to you. Here are some of the main things to consider. 

Advantages

• It can help to reduce your risk of broken bones.
• It’s available as a daily or weekly tablet. 
• It starts to work quickly and is effective for at least five years of use. 
• It keeps helping your bone strength for a while, even after you stop taking it. 

Disadvantages

• As with all medications, some people get side effects.
• There are some possible health risks after several years of use, but these are rare. 
• Tablets won’t be suitable for everyone. 

If you’ve thought carefully about the advantages and disadvantages but still feel unsure, we have more information to help guide you through deciding whether or not to have a drug treatment. 

Content reviewed: March 2023 

• electronic medicines compendium (emc). Risedronate sodium 5 mg film-coated tablets – Summary of Product Characteristics (SmPC) [Internet]. 2020 [cited 2023 Feb 19]. Available from: https://www.medicines.org.uk/emc/product/3029/smpc#gref
• electronic medicines compendium (emc). Risedronate Sodium 35 mg Film-coated Tablets – Summary of Product Characteristics (SmPC) [Internet]. 2020 [cited 2023 Feb 19]. Available from: https://www.medicines.org.uk/emc/product/4767/smpc#gref
• Hamilton B, McCoy K, Taggart H. Tolerability and compliance with risedronate in clinical practice. Osteoporos Int. 2003;14:259–62.
• Hayes KN, Brown KA, Cheung AM, Kim SA, Juurlink DN, Cadarette SM. Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy : A Propensity Score-Matched Cohort Study. Ann Intern Med. 2022;175:335–43.
• National Osteoporosis Guideline Group (NOGG). Clinical guideline for the prevention and treatment of osteoporosis. 2021.
• Waltman N, Kupzyk KA, Flores LE, Mack LR, Lappe JM, Bilek LD. Bone-loading exercises versus risedronate for the prevention of osteoporosis in postmenopausal women with low bone mass: a randomized controlled trial. Osteoporos Int. 2022;33:475–86.
• Webster RK, Weinman J, Rubin GJ. People’s Understanding of Verbal Risk Descriptors in Patient Information Leaflets: A Cross-Sectional National Survey of 18- to 65-Year-Olds in England. Drug Saf. 2017;40:743–54.
• Wells GA, Hsieh SC, Zheng C, Peterson J, Liu W, Kelly SE, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews [Internet]. 2022 [cited 2023 Feb 19]; Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004523.pub4/full

Related content:

• Getting the best from your treatment

Sandoz Risedronate – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Risedronate belongs to a group of medications called bisphosphonates. It is used to treat and prevent osteoporosis for women who are past menopause, and to treat and prevent osteoporosis caused by treatment with corticosteroids (e. g., prednisone) for men and women. It is also used to improve bone mineral density for men with osteoporosis, and to treat a condition called Paget’s disease. The long-acting form of risedronate is used only to treat osteoporosis in women who are past menopause.

Risedronate increases the thickness of bone (bone mineral density) by slowing down the cells that usually break down bone (osteoclasts). This allows the cells that build bone (osteoblasts) to work more efficiently. By making bones stronger, risedronate can help to reduce the incidence of osteoporosis-related fractures.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles.  If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Each film-coated, oval, orange tablet with “35” engraved on one face contains the equivalent of 35 mg of anhydrous risedronate sodium in the form of the hemi-pentahydrate with small amounts of monohydrate. Nonmedicinal ingredients: crospovidone, ferric oxide red, ferric oxide yellow, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide.

How should I use this medication?

For preventing osteoporosis in women who are past menopause, the recommended dose of risedronate is 5 mg once daily or 35 mg once weekly.

For treating osteoporosis in women who are past menopause, there are multiple schedules for taking risedronate. It may be taken 5 mg once daily, 35 mg once weekly, or 150 mg once a month on the same calendar day each month.

For treating osteoporosis in men, the recommended dose of risedronate is 35 mg once weekly.

For treating and preventing osteoporosis caused by treatment with corticosteroids, the recommended dose of risedronate is 5 mg daily.

For treating Paget’s disease, the recommended dose is 30 mg once daily for 2 months.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to take this medication exactly as prescribed by your doctor.

The tablet should be taken with plain water at least 30 minutes before the first food or drink of the day. It may also be taken at least 2 hours after any food or drink other than plain water. Do not eat or drink for 2 hours before and for at least 30 minutes after taking the tablet.

All strengths of risedronate should be taken while sitting in an upright position and swallowed whole (not chewed) with at least a half glass of water (i.e., at least 120 mL). Do not lie down for at least 30 minutes after taking the medication to prevent any irritation to your esophagus (the tube connecting the mouth and stomach).

If you are taking calcium supplements or aluminum-, iron-, or magnesium-containing medications (e.g., antacids and mineral supplements), you should take them at a different time of day. When taken together with risedronate, they will decrease the amount of risedronate that is delivered from your stomach into your body and reduce the effectiveness of the risedronate.

If you are taking this medication on a once-daily schedule and then miss a dose, do not take it later in the day. Resume your usual schedule the next morning. Do not take 2 doses at the same time.

If you are taking this medication on a once-weekly basis and you forget to take it on the regularly scheduled day, take one tablet on the day you first remember. Then, return to taking one tablet once a week on your regularly scheduled day. Do not take 2 tablets on the same day.

If you are taking this medication on a once-monthly basis and miss a dose and the next month’s scheduled dose is more than 7 days away, take the missed dose in the morning after the day it is remembered. If a dose is missed within 7 days of the next month’s scheduled dose, skip the missed dose and wait until the next month’s scheduled dose to continue.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take risedronate if you:

• are allergic to risedronate or any ingredients of this medication
• have low levels of calcium in the blood

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• constipation
• diarrhea
• flu-like symptoms (e.g., fever, sore throat)
• heartburn
• leg cramps
• nausea
• pain in bones, muscles, or joints
• vomiting

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• delayed healing and infection of mouth and jaw (usually after tooth extraction)
• difficulty swallowing
• new or unusual pain in the hip, groin or thigh (symptoms of fracture in the thigh bone)
• numbness, tingling, or muscle spasms (signs of low levels of calcium)
• painful tongue or mouth sores
• severe pain in bones, muscles, or joints
• signs of jaw bone problems (e. g., jaw numbness, loose teeth, exposed bone in mouth, discharge, dry mouth, gum swelling, bad breath, pain in mouth, teeth or jaw)
• vision changes or eye pain or inflammation

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of damage to the esophagus (e.g., pain in the esophagus [throat area] or behind the breastbone, chest pain, difficulty swallowing, pain when swallowing, or new or worsening heartburn)
• symptoms of a severe allergic reaction (e.g., swelling of the hands, feet, ankles, face, lips, mouth, or throat; difficulty breathing or swallowing)
• symptoms of a stomach or intestinal ulcer (e.g., nausea, vomiting, abdominal pain, loss of weight or appetite, black or bloody stools, or vomiting blood)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Atypical femur fracture: There is evidence that long-term use of this class of medication may contribute to a type of rare fracture of the long bone in the thigh (femur) without any form of trauma.

If you experience new or unusual pain in the groin, hip, or thigh area, contact your doctor as soon as possible.

Bone, joint, and muscle problems: On rare occasions, people taking this medication experience severe bone, joint, or muscle pain. This pain usually goes away when the medication is stopped.

Calcium and vitamin D: Calcium and vitamin D are important contributors to bone growth and strength. It may be necessary to take calcium or vitamin D supplements to get the best effect from risedronate if you are not getting enough from your diet. Your doctor may test you for low calcium levels or vitamin D deficiency before you start taking risedronate.

Effects on the esophagus: Risedronate can cause irritation or ulcers of the esophagus (the passage from the throat to the stomach). In some cases, these effects have been severe and have required hospitalization. Stop taking the medication and contact your doctor immediately if you suddenly experience problems swallowing, find it painful to swallow, develop pain behind the sternum (breastbone), or have new or worsening heartburn.

To reduce the risk of irritation of the esophagus, swallow this medication with a full glass of plain water first thing in the morning when you get up. Do not lie down until 30 minutes have passed and you have eaten your first food of the day. Do not chew or suck on the tablet, as this may lead to ulcers in the mouth or throat. Do not take this medication at bedtime or before getting up for the day.

Effects on the stomach and intestines: Rarely, people taking this medication have developed ulcers of the stomach or intestines. Get immediate medical attention if you have symptoms of a stomach or intestinal ulcer, such as nausea, vomiting, abdominal pain, loss of weight or appetite, black or bloody stools, or vomiting blood.

If you have a history of ulcer or other stomach problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Inflammation of the eye: Conditions of eye inflammation have been reported by people using risedronate. If you experience changes to your vision, red eyes, or eye pain, contact your doctor as soon as possible.

Jaw problems: Rarely, risedronate can cause severe jaw problems associated with delayed healing and infection, especially in people with cancer or after tooth extractions. Your doctor may ask you to see your dentist before you start taking this medication. Any necessary dental procedures should be completed before starting treatment with risedronate. It is important that you take good care of your teeth and gums while taking this medication. If you experience any mouth sores or pain in the jaw or teeth, contact your doctor as soon as possible.

Kidney function: Risedronate is removed from the body by the kidneys. Decreased kidney function may cause an increase in the amount of medication in the body, causing side effects. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Risedronate is not recommended for use by people with severely reduced kidney function.

People who cannot stand or sit upright for at least 30 minutes: This medication can cause irritation or ulcers of the esophagus (the tube connecting the mouth and stomach). People who cannot stand or sit upright for at least 30 minutes should use risedronate only if the benefits outweigh the risks.

Pregnancy: Risedronate is not intended for use during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if risedronate passes into breast milk. Risedronate is not intended for use by women who are breast-feeding. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between risedronate and any of the following:

• aminoglycoside antibiotics (e.g., amikacin, gentamicin, tobramycin)
• antacids (e.g. , aluminum hydroxide, calcium carbonate, magnesium hydroxide)
• celecoxib
• deferasirox
• h3 antagonists (e.g., famotidine, nizatidine)
• non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, ketorolac, naproxen)
• paromomycin
• proton pump inhibitors (e.g., lansoprazole, omeprazole)
• systemic angiogenesis inhibitors (e.g., axitinib, bevacizumab, lenalidomide, pazopanib, regorafenib, vandetanib)
• supplements containing minerals such as aluminum, calcium, iron, magnesium, selenium and zinc

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them.  Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2023. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Sandoz-Risedronate

Risedronic acid in the treatment of postmenopausal osteoporosis

Introduction

Osteoporosis is the most common systemic skeletal disease characterized by a decrease in bone density and a subsequent increase in the risk of fractures. The problem of osteoporosis has gained particular importance in recent years, due to the significant aging of the population and the increase in the number of women in the postmenopausal period. Nearly one in three women aged 65 years and older has at least one osteoporotic bone fracture. Osteoporotic fractures significantly affect the morbidity and mortality of the population. Due to fractures of the femur, the average life expectancy is reduced by 12-15%. The overall risk of osteoporotic fractures in women aged 50 years is 39.7%, in men — 13.1% [1, 2]. Over the past years, bisphosphonates have been most actively used in the treatment of postmenopausal osteoporosis and the prevention of its complications. The main action of bisphosphonates is aimed at slowing down the mineralization of bone tissue and inhibiting its resorption. There are currently seven classes of bisphosphonates for the treatment of bone disease: etidronate, clodronate, pamidronate, alendronate, ibandronate, risedronate, and zoledronate. The effect of various bisphosphonates on osteoclast activity varies significantly, as has been proven in numerous in vivo and in vitro studies. Risedronate, ibandronate and zoledronate were found to have the highest activity (Fig. 1).

Representatives of almost all groups of bisphosphonates, both original and generic, are used in Ukraine. There are also various forms of their administration (oral, for intravenous administration), the preference for the route of administration of bisphosphonates has an impact on the bioavailability of the drug. Thus, when taking risedronic acid, only 1-5% of the incoming substance is absorbed orally in the stomach and upper small intestine. 60% of the absorbed substance is incorporated into the bone tissue, the remaining amount (40%) is excreted in the urine.

Tolerability is important when prescribing bisphosphonates. With intravenous administration of bisphosphonates, the most common side effect is influenza-like reactions, with oral administration – adverse effects from the gastrointestinal tract: dyspepsia, epigastric pain, diarrhea. Comparative studies on the tolerance of bisphosphonates are rare. Thus, in the REAL study, the incidence of dyspepsia when taking risedronic acid was comparable to placebo, which was significantly different from the comparison group, whose patients took alendronate.

When choosing the optimal bisphosphonate in the treatment of postmenopausal osteoporosis, a significant role is also given to the socio-economic factor, and therefore the majority of patients in older age groups take generic bisphosphonates.

On the basis of the Ukrainian Scientific and Medical Center for Osteoporosis Problems, a prospective study was conducted to study the effectiveness of generic risedronate with proven bioequivalence of the active substance in the treatment of postmenopausal osteoporosis.

The efficacy and safety of risedronic acid in the treatment of primary and secondary forms of osteoporosis has been proven in many studies. S.T. Harris et al. it was found that taking risedronate reduces the incidence of new vertebral fractures already during the first year; after 12 months, the risk of vertebral fractures in the risedronate group was reduced by 65% ​​compared to the placebo group. After 3 years, compared with the placebo group, the risedronate group had a lower incidence of fractures of the vertebral bodies (p = 0.003) and other bones (p = 0.02): daily intake of 5 mg of risedronic acid in women with osteoporosis and a history of vertebral fractures resulted in reduction in the incidence of vertebral fractures by 41%, and non-vertebral fractures by 39%% compared with the control group [4]. In a study by N.B. Watts showed that the risk of new vertebral fractures remains reduced for 1 year after cessation of risedronate therapy [9]. With long-term use of risedronic acid (for 7 years), a positive effect on the incidence of fractures, bone mineral density (BMD) and markers of bone metabolism remains [5].

Study aims to evaluate the efficacy and safety of risedronic acid (Risedronic acid, Zentiva’s Sanofi Aventis) in the treatment of osteoporosis in postmenopausal women.

Object and methods of research

The study included 19 postmenopausal women with an average age of 64. 2 ± 9.2 years, an average height of 158.3 ± 5.8 cm, an average body weight of 65.1 ± 5.7 kg, and a body mass index of 26 .0 ± 5.7 kg/m2. All women were examined at the beginning of the study and after 3 months, 17 of them – after 6 months, 15 – after 9 and 12 months.

The study included women with postmenopausal osteoporosis. One of the inclusion criteria for patients in the study was a decrease in bone mineral density below 2.5 SD at the level of the lumbar spine and/or proximal spine, which, according to WHO criteria, corresponds to osteoporosis. The study did not include patients who, for therapeutic purposes during the last 3 months before the start of the study, took antiresorbents or stimulants of bone formation (calcitonin, bisphosphonates, strontium ranelate, etc.) or used drugs that affect bone metabolism; as well as patients with comorbidities in the stage of sub- or decompensation.

The severity of vertebral pain syndrome, the degree of influence of osteoporosis on physical activity and mental state, as well as the quality of life of patients were determined using unified questionnaires. The severity of vertebral pain syndrome was assessed using a four-component visual analog scale (VAS), including four 10-point subscales: pain level at the time of examination (VAS-1), average (typical) pain level (VAS-2), minimal (VAS-3 ) and maximum pain level (VAS-4). Quality of life indicators were assessed using the European Quality of Life Questionnaire (EuroQol-5D). All questionnaires were completed by the patients themselves under the supervision of a physician.

At the beginning of the study, all patients underwent a clinical and laboratory study, which included a complete blood count with a formula, a general urinalysis, a biochemical blood test, and the determination of calcium in the blood serum.

X-ray two-photon absorptiometry (DXA, Prodigy GE) was used to determine bone mineral density at the level of the entire skeleton, lumbar spine, proximal femur (general index, femoral neck, trochanter) and forearm (ultradistal region, middle third).

The duration of observation was 1 year, all studies were performed at the time of inclusion, after 3, 6, 9 and 12 months.

The patient took Rizendros 1 tablet (35 mg) once a week in the morning on an empty stomach with a glass of water (at least 120 ml) at least 30 minutes before the first meal, drink or other drug, while constantly taking the combined calcium and vitamin D preparation, 2 tablets per day (at the rate of 1000 mg / day of calcium and 600-800 IU / day of vitamin D) for 12 months.

Results

When evaluating the effect of therapy with Rizendros on the severity of vertebral pain syndrome, according to the results of VAS, a significant decrease in pain severity at the time of examination (VAS-1) after 9 and 12 months of therapy, the average level of pain – after 12 months, the minimum level – after 6 and 12 months and the maximum level of pain – after 12 months of therapy (Fig. 2).

Based on the results of studying the dynamics of the BMD index in women with postmenopausal osteoporosis for 12 months, a significant increase in BMD was found at the level of the lumbar spine and proximal femur (Fig. 3). At the level of the femoral neck, a significant increase in BMD was detected after 3, 9and 12 months of treatment. Regarding the BMD indices at the level of the bones of the forearm and the entire skeleton, a positive trend towards an increase in the indices was noted throughout the entire observation period, however, no significant differences were found.

The dynamics of BMD at the level of the lumbar spine after 3 months was 4.5%, after 6 months — 5.2%, after 12 months — 8.3% (Fig. 4).

During the study, no side effects were noted in patients taking risedronate. The analysis of laboratory and clinical indicators of deviations was not revealed.

Discussion

The results of numerous studies have confirmed the effectiveness of risedronic acid in the treatment of postmenopausal osteoporosis. Thus, most studies have shown that the use of risedronic acid in women with postmenopausal osteoporosis significantly reduced the incidence of vertebral and non-vertebral fractures compared with the placebo group [3–9]. In a study by S.T. Harris et al. it was shown that the dynamics of BMD at the level of the lumbar spine when taking risedronic acid for 3 years was 5.4% [4]; in a study by O.H. Sorensen et al. when taking risedronic acid for 5 years, the dynamics of BMD at the level of the lumbar spine was 9.3% [6]. Our results also showed a significant increase in BMD at the level of the lumbar spine and femoral neck in women with postmenopausal osteoporosis when taking risedronate. The dynamics of BMD at the level of the lumbar spine was 8.3%. The differences in this indicator can be explained by a small sample of patients compared to previous studies.

Terminals

The use of Rizendros in the treatment of postmenopausal osteoporosis is an effective and safe method of therapy. The use of the drug for 12 months leads to a significant decrease in the severity of vertebral pain syndrome, an increase in BMD at the level of the lumbar spine and femur.

References

1. Povoroznyuk V. V. Illness of the cystic-mucosal system in people of different ages (selected lectures, look around, articles): In 2 volumes – K., 2004. – 480 p.

2. Povoroznyuk V.V., Grigorieva N.V. Menopause and the musculoskeletal system. – K., 2004. – 512 p.

3. Harrington J.T., Ste-Marie L.G., Brandi M.L. et al. Risedronate rapidly reduces the risk for nonvertebral fractures in women with postmenopausal osteoporosis // Calcif. tissue int. – 2004. – 74. – P. 129-135.

4. Harris S.T., Watts N.B., Genant H.K. et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial // JAMA. – 1999. – 282 (14). – P. 1344-1352.

5. Mellström D.D., Sörensen H., Goemaere S. et al. Seven Years of Treatment with Risedronate in Women with Postmenopausal // Osteoporosis Calcif. tissue int. – 2004. – 75. – R. 462-468.

6. Sorensen O.H., Crawford G.M., Mulder H. et al. Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience // Bone. – 2003. – 32. – P. 120-126.

7. Silverman S.L., Watts N.B., Delmas P.D. et al. Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: The risedronate and alendronate (REAL) cohort study // Osteoporos Int. – 2007. – 18. – P. 25-34.

8. Siris E.S., Simon J.A., Barton I.P. et al. Effects of risedronate on fracture risk in postmenopausal women with osteopenia // Osteoporos Int. – 2008. – 19. – P. 681-686.

9. Watts N.B., Chines A., Olszynski W.P. et al. Fracture risk remains reduced one year after the discontinuation of risendronate // Osteoporos Int. – 2008. – 19. – P. 365-372.

PHARMATECA » Risedronate in the treatment of osteoporosis: efficacy and tolerability

Risedronate, belonging to the class of nitrogen-containing bisphosphonates, has a high anti-fracture activity and can reduce the risk of vertebral, non-vertebral and hip fractures in established postmenopausal osteoporosis. In terms of the number, spectrum, and severity of side effects, risedronate does not differ from other bisphosphonates.

Bisphosphonates (BP) are currently the main class of drugs used in the treatment of osteoporosis and other metabolic diseases characterized by increased bone resorption. BP has been used in clinical practice since the end of 1960s Due to the high affinity of this group of drugs for bone tissue, the following diseases/conditions are indications for their use: ectopic ossification, fibrous dysplasia, osteogenesis imperfecta, Paget’s disease, hypercalcemia due to various causes; bone metastases and multiple myeloma. In the treatment of osteoporosis, four nitrogen-containing BPs are used – alendronate, risedronate, ibandronate and zoledronic acid.

Chemical structure and mechanism of action of BF

All BPs have a similar mechanism of action due to their identical chemical structure, which is based on the pyrophosphate molecule. However, the binding ability and antiresorptive potential of the presented BPs differ due to the difference between the two side chains (Table 1).

Table 1. Chemical structure of nitrogen-containing BP side chains.

The R ¹ side chain is responsible for the affinity of BF to bone, and the R ² chain provides an antiresorptive effect. BPs with high affinity bind strongly to bone tissue, but the rate of their penetration and spread over the bone surface is low. BPs with low affinity are more widely distributed, and the period of their stay in the bone after the cessation of treatment is shorter. These features may explain differences in the rate of onset of the antifracture effect, duration of action, frequency of side effects, etc.

Nitrogen-containing BPs inhibit a specific enzyme found in osteoclasts called “farnesyl pyrophosphate synthase”. If the BPs are placed in a specific sequence based on their effect on farnesyl pyrophosphate synthase inhibition, the sequence would be: zoledronate-risedronate-ibandronate-alendronate. Thus, heterocyclic BPs (zoledronate and risedronate) have a large antiresorptive effect.

BF suppress increased bone resorption. This result is fast, and the most pronounced decrease in bone resorption is observed after 3-6 months from the start of therapy, and can persist for 10 years or longer while the drug is used. This effect of BP is associated with an increase in bone mineral density (BMD), which is associated with a decrease in the risk of fractures.

Peculiarities of BP pharmacokinetics

Currently, there are two ways of using BP – orally and intravenously. The intake of BF inside is associated with a number of circumstances due to their pharmacokinetics and pharmacodynamics. BF in tablet form should be taken after a long fast (usually in the morning – about 6-8 hours after the last meal) to ensure better absorption in the gastrointestinal tract (GIT). Under these conditions, less than 1% of the active substance can be absorbed. When taking BF with food, their absorption can be completely blocked. The half-life of BP is short. 40-60% of the absorbed dose binds to bone tissue, primarily in areas of the skeleton with active remodeling. The rest of the active substance is rapidly excreted by the kidneys. In the gastrointestinal tract, BP is not metabolized and is excreted unchanged in the feces.

Stable bone levels of risedronate are achieved 57 days after initiation of therapy. The half-life of the drug in women with postmenopausal osteoporosis is 561 hours [13].

It is believed that when BP is used parenterally, 100% of the administered dose binds to bone tissue.

The effect of BP on the risk of fractures of various locations

To prove the ability of anti-osteoporotic drugs to significantly reduce the risk of fractures, randomized clinical trials (RCTs) of high statistical power are being conducted. As a rule, RCTs that show the effect of an investigational drug on the risk of vertebral fractures are planned first, since it is enough to include approximately 1000 patients in the study, and it is not difficult to establish the presence of compression fractures using X-ray morphometry. Since the incidence of hip fractures is significantly lower than that of vertebral fractures in the general population, more patients with osteoporosis (6000-8000) should be included in RCTs to obtain statistically significant positive results. To assess the effect of anti-osteoporotic drugs on the risk of all nonvertebral fractures, RCTs alone are not enough; therefore, conclusions on this issue are made on the basis of meta-analyses, systematic reviews, and other pooled studies (Table 2).

Table 2. Randomized clinical trials demonstrating the anti-fracture effect of BP .

Of all the CFs registered for the treatment of postmenopausal osteoporosis, only three of them (alendronate, risedronate and zoledronic acid) have evidence to reduce the risk of hip fractures. The risks of non-vertebral fractures were also reduced with the use of these three BPs.

Analysis of the literature allowed various national scientific societies and associations to formulate the main indications for the prevention and treatment of primary and secondary osteoporosis with BP (Table 3).

Table 3. Range of indications for BP for the prevention and treatment of osteoporosis.

Review of risedronate clinical trials

In two 3-year RCTs, risedronate 2.5 or 5.0 mg daily was given concomitantly with 1000 mg calcium and 500 IU vitamin D in postmenopausal women with established osteoporosis and a history of vertebral fractures (3684 people). Criteria for inclusion in the study:

• age not older than 85 years;
• duration of menopause 5 years or more;
• having 2 or more radiographically confirmed vertebral fractures or 1 vertebral fracture and a decrease in BMD ≤-2 SD on T-score.

Already a year later, the frequency of new vertebral fractures decreased by 62% compared with the control, the frequency of fractures of other localization within 3 years decreased by 33-39% (level A) [4, 10]. However, patients treated with risedronate 2.5 mg/day were subsequently excluded from the analysis due to the low efficacy of the dose used.

A 2001 Cochrane review aimed to determine the potential of risedronate to prevent the risk of hip fracture in elderly women [7]. The patients were divided into two groups. The first group included women aged 70-79 years with BMD by T-score < -4.0 SD or T-score < -3.0 SD and the presence of one or more risk factors for hip fracture. The second group consisted of patients older than 80 years, while BMD did not have to meet the criteria for osteoporosis. Treatment with risedronate continued for 3 years at a dose of 2.5; 5 mg/day, the control group received a placebo. In total, 3624 patients were in the main group, 1821 in the placebo group. The main group of patients older than 80 years consisted of 2573 women, the placebo group - of 1313.years, there was a decrease in the absolute risk of hip fracture by 1.3%, which corresponded to an NNT of 77 (p = 0.009). The NNT indicator has become quite often used to prove the effectiveness of drug therapy. NNT (Number Need to Treat) indicates how many patients need to be treated to prevent one adverse event/fracture. In women with verified vertebral fractures, the reduction in the absolute risk of hip fracture was 3.4%, and the NNT was 29(p = 0.003).

An additional (post-hoc) analysis of the HIP clinical trial (Hip Intervention Program) was conducted, which included patients of older age groups (≥70 years) with a confirmed diagnosis of osteoporosis based on a T-score of the femoral neck ≤-2.5 SD and the presence of at least one vertebral fracture [11]. The power of analysis was 1656 women, of whom 1090 received risedronate and 566 received placebo. After 3 years of follow-up, 7.4% of patients in the placebo group had a hip fracture, and only 3.8% in the risedronate group. Thus, the absolute risk of hip fracture decreased by 3.6%, and NNT was 28.95 (p = 0.019). The analysis included 704 patients treated with risedronate and 688 treated with placebo (mean age 83 years). This study also re-confirmed that risedronate was effective in reducing the risk of vertebral fractures.

Pooled analysis of RCTs by J. T. Harrington et al. (2004), showed that risedronate statistically significantly reduced the risk of non-vertebral fractures as early as 6 months from the start of therapy, but not hip fractures [12].

A Cochrane review (2008) pooling data from 7 RCTs on the use of risedronate to reduce the risk of fracture in postmenopausal women showed that 100 patients need to be treated to prevent 1 hip fracture [13]. However, risedronate has not been shown to prevent hip fractures in individuals who do not have a decrease in BMD and no vertebral fractures.

Head-to-head studies between anti-osteoporotic drugs allow judgments about their greater or lesser effectiveness, as well as differences in tolerability. The limitations of such a few studies are due to the fact that so-called. surrogate measures such as BMD and biochemical markers of bone metabolism rather than fracture risk.

An example of a direct comparative prospective study is the FACT study, which included 1053 postmenopausal women who received alendronate 70 mg and risedronate 35 mg weekly for a year. A more pronounced increase in BMD in various parts of the skeleton was observed among patients in the alendronate group [14]. However, differences in the level of increase in BMD cannot indicate the strength of the anti-fracture effect of any of the anti-osteoporotic drugs.

Additional information about anti-osteoporotic drugs can be obtained from retrospective studies reflecting their effectiveness in real clinical practice. However, in retrospective studies, it is not possible to assess the impact on the results of the degree of adherence of patients to the prescribed drug therapy. Thus, a study conducted in 2008 by a group of authors led by S.M. Cadarette, included an analysis of 41,135 clinical cases taken from the database of the state insurance company [15]. There were no statistically significant differences in the number of hip fractures between groups of patients treated with alendronate or risedronate for 2 years.

Another retrospective study (REAL) included 21,615 women aged 65 years and older who received alendronate and 12,215 women who received risedronate once a week [16]. Risedronate was associated with fewer hip fractures. However, it should be noted that the alendronate group received both 35 and 70 mg per week of alendronate. Alendronate 35 mg/week is known to have been used to prevent osteoporosis, while risedronate 35 mg/week has been used for both prevention and treatment of osteoporosis.

Another retrospective REALITY trial included 12,956 women over 65 who were prescribed alendronate and 6,107 patients who were treated with risedronate. It was found that patients treated with risedronate had one additional fracture per 200 patient-years compared with the alendronate group. However, the overall risk of fractures was similar in both groups [17].

Meta-analyses of RCTs and systematic reviews provide insight into the effect of various anti-osteoporotic drugs on the relative risk of fracture. However, given the difference in study design, it is difficult for the patient population to decide on the strength of the antifracture effect of a particular drug. Alendronate and risedronate were comparable in terms of reduction in the relative risk of fractures. 9H. Taggart et al. (2002) in order to study adverse events (AEs) from the gastrointestinal tract. The analysis included 5020 patients who received risedronate at a dose of 5 mg / day, 5048 patients were included in the placebo group. Both groups were comparable in terms of the number and name of gastrointestinal diseases, the use of antisecretory drugs, aspirin and other non-steroidal anti-inflammatory drugs. During the observation period, AEs from the upper gastrointestinal tract were observed in 29.8% of cases (risedronate group) and 29.6% of cases (placebo group). Thus, the frequency of AE in the first group was 20.0, and in the second – 19.2 cases per 100 patient-years (p = 0.3). At the same time, among the patients of the risedronate group, there was no increase in clinical symptoms from the gastrointestinal tract. According to the results of the performed fibrogastroscopy, no differences were found between the two compared groups [18].

In clinical practice, it is often necessary to decide on the possible appointment of a BP in case of already existing intolerance to another. From this point of view, data from a small power study of risedronate tolerability should be cited, when any AEs from the upper gastrointestinal tract were recorded in patients against the background of alendronate use [19]. Sixty-six menopausal women were divided into two groups: the first included 35 patients who received risedronate at a dose of 5 mg/day; the second group, which consisted of 31 patients, was a placebo. The frequency of endoscopically confirmed gastric ulcers in the group of patients treated with alendronate was significantly higher (13.2%) compared with the control group treated with risedronate (4.1%). Only four patients discontinued risedronate and five alendronate. Thus, the number of patients who continued treatment with BP did not differ.

Atypical hip fracture

FDA (Food and Drug Administration) in October 2010 reported a risk of atypical hip fracture (subtrochanteric or diaphyseal) among patients taking BP for osteoporosis [20]. These types of fractures are rare and occur in less than 1% of all femoral fractures in the general population, including hip fracture. In a study published by the Atypical Hip Fracture Task Force in 2010, out of 169120 fractures developed after oral alendronate monotherapy and only 12 during risedronate therapy. One patient received risedronate after alendronate, two patients received alendronate before risedronate, and others received etidronate before risedronate [21]. The average duration of taking BF was 7 years. The Working Group confirmed that the incidence of atypical hip fractures associated with BP intake is very low. Moreover, a causal relationship of atypical hip fractures with BP intake has not been conclusively established. However, it is assumed that the risk of atypical fractures increases with the duration of BP use.

Atrial fibrillation

A pooled analysis of a phase 3 RCT aimed to investigate the effect of risedronate on the incidence of atrial fibrillation, cardiovascular events, and death. The study included 15 thousand patients who took risedronate for 2 years [22]. There were no statistically significant differences in these AEs between risedronate and placebo.

Nephrotoxicity

Decreased creatinine clearance < 30 ml/min is a contraindication to the use of risedronate, as with other BPs, regardless of the route of administration. A retrospective analysis of 9Phase 3 RCT in which patients received risedronate 5 mg/day for 2 years. AEs associated with impaired renal function were similar between the placebo and risedronate group [23].

Osteonecrosis of the mandible

Osteonecrosis of the mandible (ONJ) ​​has been associated with the use of high doses of intravenous BP for bone malignancies. At the same time, isolated cases of ONJ are described in the literature when taking BP orally for osteoporosis [24]. According to the American Dental Association, ONJ is rare, occurring in approximately 0. 7 patients per 100,000 patient-years with alendronate. A similar risk of ONJ is expected to be associated with other nitrogen-containing BPs, including risedronate. In order to prevent ONJ, you should stop taking BP approximately 3 months before the proposed surgical intervention in the oral cavity [25].

Neoplasms of the upper gastrointestinal tract

There is evidence of a possible increased risk of esophageal cancer in patients receiving BP. In this regard, the results of a review based on a database of 41,826 patients (UK General Practice Research Database, 2010) should be cited. There were no differences in the incidence of gastric and esophageal cancer in groups of patients who received and did not receive BP [26]. Thus, there is no convincing evidence of a possible association between BP intake and esophageal cancer.

Musculoskeletal pain

RCT data suggest that intravenous BP use may be associated with musculoskeletal pain [27]. A retrospective analysis of 26,545 veterans over the age of 65 found no association between BP intake and the development of musculoskeletal pain.

Inflammatory eye diseases

There is a case report of bilateral anterior uveitis in a patient treated sequentially with alendronate and risedronate for 6 months. These phenomena completely disappeared after discontinuation of therapy [28]. Database analysis did not confirm an increased risk of uveitis/scleritis in patients treated with BP (relative risk [RR] = 1.23; 95% confidence interval [CI] – 0.85-1.79) [29].

Dermatological manifestations

The following skin changes associated with risedronate have been described: rash (1-10 cases per 1000), skin pruritus (1-10 cases per 10,000) and urticarial / bullous reaction / angioedema / photosensitivity (< 1 case per 10 thousand) [30].

Hepatotoxicity

BP-induced hepatotoxicity has been described in association with alendronate [31]. The mechanism of action of BP on the liver parenchyma is not clear. There are no large pooled data on this issue.

Hypersuppression of bone remodeling

Most RCTs examine the effect of BP on the state of bone metabolism based on the dynamics of biochemical markers. One of the negative effects of BP on bone tissue is a pronounced suppression of bone resorption, which can lead to the formation of the so-called. frozen bone. Extended clinical trials with alendronate (up to 10 years) [32] and risedronate (up to 7 years) [33] did not reveal any new side effects, including hypersuppression of bone remodeling. At the same time, the risk of vertebral fractures significantly decreased with the use of BP.

Conclusion

Risedronate, belonging to the class of nitrogen-containing BP, has a high anti-fracture activity and can reduce the risk of vertebral, non-vertebral and hip fractures in established postmenopausal osteoporosis. In terms of the number, spectrum and severity of side effects, risedronate does not differ from other BPs.

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