Osteoporosis Medications: Types, Benefits & Side Effects

What Are the Different Types of Osteoporosis Medications?

Osteoporosis medications fall into two main categories: antiresorptive drugs that slow bone breakdown (bisphosphonates, denosumab) and anabolic drugs that stimulate new bone formation (teriparatide, romosozumab). Your doctor will choose the best option based on your fracture risk, other health conditions, and treatment goals.

Osteoporosis occurs when bones become fragile and prone to fractures. The skeleton is constantly being remodeled throughout life, with old bone being broken down by cells called osteoclasts and new bone being formed by cells called osteoblasts. In osteoporosis, this balance is disrupted, with bone breakdown exceeding bone formation. Understanding this process is key to understanding how different medications work.

The goal of osteoporosis treatment is to reduce fracture risk, which is achieved either by slowing down bone resorption (breakdown) or by stimulating new bone formation. The specific medication chosen depends on several factors, including how high your fracture risk is, what symptoms you have, your age, kidney function, and whether you're taking other medications that might interact.

There are several product options for each medication type, each containing different active ingredients. Your pharmacist can provide more information about specific products, and you can find detailed prescribing information through official drug databases. Regular follow-up with your doctor is essential to monitor treatment effectiveness and adjust as needed.

Antiresorptive medications

These medications work by inhibiting osteoclasts, the cells responsible for breaking down bone tissue. By slowing bone resorption, they help maintain bone density and reduce fracture risk. The main antiresorptive medications include:

• Bisphosphonates - the most commonly prescribed class, including oral tablets (alendronate, risedronate) and IV infusions (zoledronic acid)
• Denosumab - a biologic medication given as an injection every six months

Anabolic medications

These medications actively stimulate bone formation by promoting the activity of osteoblasts. They are typically reserved for patients with severe osteoporosis or very high fracture risk:

• Teriparatide - a synthetic form of parathyroid hormone, given as daily injections for up to 2 years
• Romosozumab - a newer medication that both stimulates bone formation and reduces bone breakdown, given as monthly injections for 1 year

Treatment monitoring

Your doctor should see you annually to review blood tests and discuss ongoing treatment. Bone density scanning may be appropriate when treatment is being started or stopped, helping to track your response to medication and guide treatment decisions. This regular monitoring ensures you're receiving the most effective treatment with minimal side effects.

Potential side effects

All medications can cause unwanted effects. Some people experience side effects from osteoporosis treatment while others do not. Side effects often diminish over time as your body adjusts to the medication. If you experience troublesome side effects, speak with your doctor as you may need to try a different treatment approach. Never stop your medication without consulting your healthcare provider first.

How Do Bisphosphonates Work?

Bisphosphonates are the most commonly prescribed osteoporosis medications. They work by inhibiting osteoclasts (cells that break down bone), reducing bone loss and maintaining bone density. Their effects persist in the skeleton even after stopping treatment, making them effective for long-term fracture prevention.

Bisphosphonates are a class of drugs that bind strongly to bone mineral, where they remain for years and continue to inhibit bone resorption. This unique property means their bone-protective effects persist even after you stop taking the medication, unlike other osteoporosis treatments. Bisphosphonates have been used for decades and have an excellent track record for reducing fractures of the spine, hip, and other sites.

The mechanism of action involves bisphosphonates being incorporated into bone during the normal remodeling process. When osteoclasts attempt to break down bone containing bisphosphonates, the drug interferes with their cellular machinery, effectively reducing their ability to resorb bone. This leads to a gradual increase in bone density and improved bone strength over time.

For patients with osteoporosis and elevated fracture risk, bisphosphonates are often the first-line treatment choice. They have demonstrated excellent efficacy in preventing fractures in large clinical trials. Most patients tolerate bisphosphonates well when taken correctly, and serious side effects are rare when used at standard osteoporosis doses.

Intravenous bisphosphonates

Zoledronic acid is a potent bisphosphonate administered as an intravenous infusion directly into the bloodstream. It is typically given once yearly for three to five years. The dosing schedule may differ if you're receiving zoledronic acid for other conditions.

IV treatment is particularly suitable for patients with high fracture risk, those who have difficulty swallowing tablets, or those with memory difficulties that make adherence to oral medication regimens challenging. The advantage of yearly dosing is guaranteed compliance, and patients don't need to worry about the strict fasting requirements of oral bisphosphonates.

Oral bisphosphonates

Several bisphosphonates are available in tablet form. The most commonly used are tablets containing alendronate or risedronate. The typical regimen is one tablet once weekly, though monthly options are also available for some bisphosphonates.

Oral bisphosphonates are highly effective when taken correctly. They represent the most affordable osteoporosis treatment option and have decades of safety data supporting their use. Most patients who can follow the administration requirements do well with oral therapy.

Important administration instructions

If you take oral bisphosphonates, following these instructions is crucial for both effectiveness and safety:

• Take on an empty stomach: Take the tablet first thing in the morning, at least 30 minutes before eating breakfast or taking other medications
• Use only plain water: Swallow the tablet whole with a full glass of plain water. The medication won't work properly if taken with food, other drinks, or other medications
• Stay upright: Sit or stand when taking the tablet and avoid lying down for at least 30 minutes until after you've eaten breakfast. The active ingredient can irritate the esophagus, and lying down increases this risk
• Don't take if you can't stay upright: Do not take bisphosphonates if you cannot sit or stand for 30 minutes or have difficulty swallowing

Side effects of bisphosphonates

Some people experience stomach problems such as abdominal pain or nausea. Other side effects include headache, dizziness, or pain in muscles and joints. These are usually mild and often improve with continued use.

With IV zoledronic acid infusions, you may experience flu-like symptoms including fever, headache, and muscle aches during the first few days after treatment. You can prevent or minimize these symptoms by taking acetaminophen (paracetamol) at the time of infusion. The risk of flu-like symptoms is greatest after the first treatment and typically decreases with subsequent infusions.

Contact your doctor if you experience troublesome side effects.

What Is Denosumab and How Does It Work?

Denosumab is a biologic medication that inhibits bone breakdown by blocking RANKL, a protein essential for osteoclast formation and function. Unlike bisphosphonates, its effects wear off quickly if treatment is stopped, which can lead to rapid bone loss and increased fracture risk. Therefore, denosumab typically requires lifelong treatment.

Denosumab works through a different mechanism than bisphosphonates. It is a monoclonal antibody that targets RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand), a protein that is essential for the development, function, and survival of osteoclasts. By blocking RANKL, denosumab effectively "turns off" the cells responsible for breaking down bone.

The key difference between denosumab and bisphosphonates is what happens when treatment stops. While bisphosphonates remain in bone for years after discontinuation, denosumab's effects disappear rapidly once the medication leaves your system. This means that if you stop denosumab without transitioning to another treatment, you may quickly lose bone mass and face an increased risk of fractures - particularly vertebral fractures.

Because of this rebound effect, denosumab is typically considered a lifelong treatment commitment. If discontinuation is necessary, most guidelines recommend transitioning to bisphosphonate therapy to protect against rapid bone loss. This decision should always be made in consultation with your healthcare provider.

When is denosumab recommended?

Denosumab is often used when bisphosphonates are not suitable or cannot be tolerated. It is also preferred for patients with kidney impairment, as bisphosphonates are eliminated through the kidneys and may not be safe for those with poor kidney function.

The medication is also a good choice for patients who prefer less frequent dosing or who have difficulty with the strict administration requirements of oral bisphosphonates. Its consistent absorption regardless of food intake can be advantageous for some patients.

How is denosumab given?

Denosumab is given as a subcutaneous injection every six months. Because it requires lifelong treatment, adherence to the dosing schedule is critically important. Missing doses or delaying treatment can lead to rapid bone loss between doses.

Special considerations

If you have reduced kidney function, you have a higher risk of developing low blood calcium levels (hypocalcemia). Your doctor will check calcium levels with blood tests before and after you receive your medication. You may need additional calcium supplements or medication to help your body absorb calcium better.

Side effects of denosumab

Side effects that may occur include pain in bones or muscles. Less commonly, you may experience urinary tract symptoms.

Skin infections can occur but are less common. Contact your doctor if you notice signs of skin infection.

As with bisphosphonates, atypical femoral fractures and osteonecrosis of the jaw are rare but possible. Early symptoms of atypical fractures include pain or discomfort in the thigh, groin, or hip. If your dentist identifies jaw problems, inform your osteoporosis physician. The risk of jaw complications is higher with certain other conditions, jaw injuries, or use of certain other medications.

Dental procedures

If you need surgery or tooth extraction from your dentist, it's important to inform them that you take denosumab. They can take extra care monitoring wound healing. Do not stop denosumab treatment because you need dental care - discuss how to proceed with your doctor.

When Is Teriparatide Used?

Teriparatide is an anabolic medication that stimulates bone formation by mimicking parathyroid hormone. It is reserved for patients with severe osteoporosis and very high fracture risk, particularly those who have already had multiple fractures or have very low bone density. Treatment is limited to a maximum of 2 years.

Teriparatide represents a fundamentally different approach to osteoporosis treatment. Rather than simply slowing bone breakdown like bisphosphonates and denosumab, teriparatide actively stimulates the cells that build new bone (osteoblasts). This makes it particularly valuable for patients who have already experienced significant bone loss and need to rebuild bone mass.

The medication is a synthetic form of parathyroid hormone, which naturally regulates calcium and bone metabolism in the body. When given in the specific pulsatile pattern of daily injections, parathyroid hormone has a net anabolic (bone-building) effect. Continuous exposure to parathyroid hormone would actually break down bone, but the daily injection pattern produces the opposite effect.

Clinical trials have demonstrated that teriparatide significantly reduces vertebral and non-vertebral fracture risk. Patients often experience measurable increases in bone density, particularly in the spine. The medication is especially effective at rebuilding trabecular bone, the spongy bone tissue that makes up the interior of vertebrae.

Who is suitable for teriparatide?

Treatment with teriparatide may be considered if you have severe osteoporosis and a very high risk of fractures. This typically includes patients who already have multiple fractures and very low bone density. You may also receive this medication if you have had several new serious fractures despite treatment with another osteoporosis medication. Treatment is managed by specialist physicians.

Teriparatide is not recommended as first-line therapy for most patients with osteoporosis due to its cost, the need for daily injections, and the limited treatment duration. However, for appropriately selected high-risk patients, it can provide significant benefits that other medications cannot achieve.

How is teriparatide given?

You self-administer the medication as a subcutaneous injection daily. The injection is given using a pre-filled pen device, similar to insulin pens used by diabetics. Most patients can learn to give themselves the injections after initial training.

The treatment duration is limited to a maximum of two years, after which treatment continues with bisphosphonates or denosumab to maintain the bone gains achieved. The sequential approach - building bone with teriparatide then maintaining it with antiresorptive therapy - can provide optimal long-term fracture protection.

Side effects of teriparatide

Some people using teriparatide may experience side effects such as nausea, dizziness, or muscle cramps. Some patients may experience headache or fatigue.

A temporary drop in blood pressure can occur after injection, causing lightheadedness. For this reason, it's recommended to sit or lie down for the first few doses until you know how you'll react. These effects usually diminish with continued use.

What Is Romosozumab?

Romosozumab is the newest osteoporosis medication that has a unique dual action: it both stimulates bone formation and inhibits bone breakdown simultaneously. It is given as monthly injections for one year and is reserved for patients with severe osteoporosis at very high fracture risk.

Romosozumab works by blocking sclerostin, a protein produced by bone cells that normally inhibits bone formation and promotes bone breakdown. By blocking sclerostin, romosozumab unleashes the bone-building potential of osteoblasts while simultaneously reducing osteoclast activity. This dual mechanism results in rapid increases in bone density.

Clinical trials have shown that romosozumab produces larger and faster increases in bone density than other osteoporosis medications. It significantly reduces both vertebral and non-vertebral fractures. The dramatic bone-building effect makes it particularly valuable for patients with very severe osteoporosis who need rapid improvement in bone strength.

The medication represents an important advance for patients at the highest fracture risk, offering benefits that cannot be achieved with other medications. However, it also comes with specific considerations regarding cardiovascular risk that must be evaluated before starting treatment.

Who should consider romosozumab?

Treatment with romosozumab may be considered if you have severe osteoporosis and a very high risk of fractures. This may include patients who have already had a hip or vertebral fracture and have very low bone density.

Your doctor will carefully assess whether romosozumab is appropriate for you, considering factors including your cardiovascular health. Romosozumab is not recommended for patients with a history of heart attack or stroke within the past year, as clinical trials suggested a possible increased cardiovascular risk.

How is romosozumab given?

You self-administer the medication as a subcutaneous injection in each thigh once monthly. Two separate injections are given each month - one in each thigh. Treatment duration is one year, after which treatment continues with bisphosphonates or denosumab to maintain the bone gains.

Treatment is managed by specialist physicians who have experience with osteoporosis and can monitor for potential complications. Regular follow-up is essential during and after romosozumab treatment.

Side effects of romosozumab

Some people using romosozumab may experience side effects such as joint pain, headache, or redness or tenderness at the injection site.

As with other potent osteoporosis medications, there is a small risk of atypical femoral fractures and osteonecrosis of the jaw. Report any unusual thigh or groin pain to your doctor, and inform your dentist about your medication before dental procedures.

Why Are Calcium and Vitamin D Important?

Calcium and vitamin D supplements are commonly prescribed alongside osteoporosis medications to support treatment effectiveness. Calcium is essential for building bone, while vitamin D increases calcium absorption from the gut. Without adequate calcium and vitamin D, osteoporosis medications cannot work optimally.

While osteoporosis medications work to reduce bone breakdown or stimulate bone formation, they cannot build strong bone without the raw materials - primarily calcium. Calcium is the mineral that gives bones their strength and rigidity. About 99% of your body's calcium is stored in bones and teeth.

Vitamin D plays a crucial supporting role by increasing the body's ability to absorb calcium from food. Without adequate vitamin D, even a calcium-rich diet may not provide enough absorbable calcium. When blood calcium levels fall too low, the body compensates by taking calcium from the skeleton, which is counterproductive to osteoporosis treatment.

Most clinical trials of osteoporosis medications included calcium and vitamin D supplementation as part of the treatment protocol. The impressive fracture reduction seen in these trials was achieved with the combination of specific osteoporosis medication plus adequate calcium and vitamin D. This is why most treatment guidelines recommend supplementation alongside osteoporosis medications.

However, calcium and vitamin D supplements alone do not significantly reduce fracture risk for prevention purposes. They are best viewed as essential adjuncts to osteoporosis medications rather than treatments in their own right. If your dietary calcium intake is high, you may need only vitamin D supplementation. Discuss what's best for you with your doctor.

Important considerations before starting

Before you start taking calcium and vitamin D, your doctor will check your blood calcium levels and kidney function. If you have a history of kidney stones, additional calcium supplementation may increase the risk of new stone formation. Always discuss your complete medical history with your doctor before taking supplements.

Adequate calcium intake can often be achieved through diet, particularly dairy products, fortified foods, and certain vegetables. Your doctor can help determine whether you need supplements based on your dietary intake and individual needs.

Side effects

Side effects are uncommon, but the most frequent include digestive symptoms, particularly constipation and nausea. Taking calcium supplements with food and adequate water can minimize these effects. If constipation is problematic, different calcium formulations may be better tolerated.

How Do Doctors Choose the Right Medication?

The choice of osteoporosis medication depends on your fracture risk level, previous fracture history, bone density measurements, kidney function, other health conditions, ability to take oral medications, and personal preferences. First-line treatment for most patients is oral bisphosphonates, while injectable options are reserved for those who cannot tolerate or absorb oral medications.

Selecting the most appropriate osteoporosis medication is a personalized decision that your doctor will make based on multiple factors. There is no single "best" medication - the optimal choice depends entirely on your individual circumstances and needs.

For most patients with osteoporosis, oral bisphosphonates (alendronate or risedronate) are the first choice. They have decades of safety data, are highly effective at preventing fractures, and are the most affordable option. The main requirements are that you can swallow tablets, tolerate the gastrointestinal effects, and comply with the specific administration requirements.

If oral bisphosphonates are not suitable, IV zoledronic acid offers similar efficacy with yearly dosing. This is particularly useful for patients with swallowing difficulties, upper GI problems, or adherence challenges. Denosumab is another option for patients who cannot take bisphosphonates, particularly those with kidney impairment.

For patients at very high fracture risk - typically those with multiple prior fractures and very low bone density - anabolic medications (teriparatide or romosozumab) may be considered. These medications actively build bone and may be more appropriate when rapid improvement in bone strength is needed.

Factors influencing treatment choice

• Fracture risk: Higher risk may warrant more potent medications
• Previous fractures: History of fractures, especially multiple or recent, influences treatment intensity
• Bone density: Very low T-scores may favor anabolic agents
• Kidney function: Impaired kidneys may preclude bisphosphonates
• Gastrointestinal health: Esophageal problems may preclude oral bisphosphonates
• Cardiovascular history: Recent heart attack or stroke may affect romosozumab eligibility
• Patient preference: Frequency and route of administration matter to many patients
• Cost and access: Newer medications are more expensive and may not be covered by all insurance plans

How Is Osteoporosis Treatment Monitored?

Osteoporosis treatment is typically monitored through annual clinical reviews, periodic blood tests, and bone density scans. Blood tests may include calcium, vitamin D, and bone turnover markers. Bone density scans help track response to treatment and guide decisions about continuing, changing, or stopping medication.

Regular monitoring is essential to ensure your osteoporosis treatment is working effectively and to identify any complications early. Most patients should see their doctor at least annually for a comprehensive review of their treatment.

Annual visits typically include discussion of any new fractures or symptoms, review of medication adherence and tolerance, and blood tests. Bone density scanning may be repeated periodically, typically every 2-3 years during treatment, though the exact interval depends on your individual circumstances and the specific medication you're taking.

Bone density scans are particularly important at the time treatment decisions are being made - when starting, changing, or stopping medication. They provide objective evidence of whether your bones are responding to treatment and help guide long-term management decisions.

Treatment duration and drug holidays

For bisphosphonates, treatment is typically continued for 3-5 years, after which your doctor will reassess whether continued treatment is necessary. Some patients at lower risk may be able to take a "drug holiday" - a period off medication during which the residual effect of bisphosphonates continues to protect bones. Higher-risk patients may need to continue treatment or switch to an alternative medication.

Denosumab does not allow for drug holidays due to the rebound bone loss that occurs when it is stopped. Patients on denosumab typically need to continue treatment indefinitely or transition carefully to bisphosphonates under medical supervision.