What medications can cause bone loss? A comprehensive guide to drug-induced osteoporosis

Glucocorticoids, such as prednisone, are among the most common causes of drug-induced osteoporosis, but many other widely used medications also contribute to bone weakening. Understanding what medications can cause bone loss is crucial for patients and healthcare providers to mitigate risks and protect long-term bone health.

Quick Summary

Certain medications, including steroids, proton pump inhibitors, and some cancer therapies, are known to increase fracture risk by interfering with bone metabolism. Being aware of these drug classes is essential for preventing or managing drug-induced bone loss and protecting skeletal health.

Key Points

• Glucocorticoids are a primary cause: Medications like prednisone are a leading cause of drug-induced osteoporosis due to their effect on bone formation and resorption.

• Hormone therapies impact bone density: Breast cancer treatments (aromatase inhibitors) and prostate cancer treatments (ADT) can significantly accelerate bone loss by suppressing sex hormones.

• Long-term PPI use poses a risk: Chronic use of proton pump inhibitors for heartburn is associated with an increased risk of hip fractures, possibly due to reduced calcium absorption.

• Some antidepressants can affect bones: Selective serotonin reuptake inhibitors (SSRIs), when taken long-term, have been linked to lower bone mineral density and increased fracture risk.

• Anticonvulsants interfere with vitamin D: Older antiepileptic drugs can disrupt vitamin D metabolism, leading to decreased calcium absorption and weakened bones.

• Excess thyroid medication is harmful: Over-supplementing thyroid hormone can cause hyperthyroidism, which accelerates bone turnover and leads to bone loss.

• Mitigation strategies are available: Regular monitoring, calcium and vitamin D supplementation, and weight-bearing exercise are crucial for those at risk of medication-induced bone loss.

Understanding Bone Remodeling

Bone is a living, active tissue that is constantly being broken down and rebuilt in a process called remodeling. This continuous process is essential for maintaining strong, healthy bones. Specialized cells called osteoclasts resorb, or break down, old bone tissue, while osteoblasts form new bone. A proper balance between resorption and formation is critical. When certain medications disrupt this balance, it can lead to more bone being lost than replaced, resulting in drug-induced osteoporosis.

Medications with a High Risk of Causing Bone Loss

Glucocorticoids (Corticosteroids)

Glucocorticoids are arguably the most common cause of medication-induced osteoporosis and are used to treat a wide array of conditions, including rheumatoid arthritis, asthma, inflammatory bowel disease, and autoimmune disorders. Their effects are dose- and duration-dependent, with significant bone loss occurring within the first year of oral therapy.

• How they cause bone loss: Glucocorticoids inhibit osteoblast function, increase osteoclast activity, and interfere with calcium absorption and vitamin D metabolism. This leads to rapid bone mineral density (BMD) decline and heightened fracture risk.
• Examples: Prednisone, dexamethasone, cortisone.

Hormone-Related Cancer Therapies

Many hormone-related cancer treatments, which work by suppressing or blocking sex hormones, can have significant adverse effects on bone health.

• Aromatase Inhibitors (AIs): Used to treat hormone-receptor-positive breast cancer in postmenopausal women, AIs reduce estrogen levels, which are protective of bone. This accelerates bone loss, increasing fracture risk.
• Androgen Deprivation Therapy (ADT): Prescribed for prostate cancer, ADT reduces testosterone levels in men. Because testosterone helps maintain bone density, this treatment can lead to significant bone loss and increased fracture risk.
• Examples: Anastrozole (Arimidex), letrozole (Femara) for AIs; leuprolide (Lupron) and goserelin (Zoladex) for ADT.

Antiepileptic Drugs (AEDs)

Some older AEDs have a well-documented link to reduced bone mineral density and higher fracture risk, though mechanisms are complex and may differ between drugs.

• How they cause bone loss: Certain AEDs accelerate the breakdown of vitamin D in the liver, leading to lower calcium absorption. They can also directly affect bone-forming cells.
• Examples: Phenytoin (Dilantin), phenobarbital, and carbamazepine (Tegretol) are most often cited.

Other Drug Classes Linked to Bone Loss

Proton Pump Inhibitors (PPIs)

Commonly used to treat acid reflux and ulcers, long-term use of PPIs has been associated with an increased risk of hip, wrist, and spine fractures.

• How they cause bone loss: The primary hypothesis is that PPIs reduce stomach acid so significantly that the absorption of calcium from food is impaired.
• Examples: Omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid).

Selective Serotonin Reuptake Inhibitors (SSRIs)

These antidepressants are widely used, but studies show an association between chronic use and lower BMD and increased fracture risk, particularly in older adults.

• How they cause bone loss: The exact mechanism is not fully understood but is thought to involve the disruption of serotonin's role in bone metabolism, potentially impacting bone cell function.
• Examples: Fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil).

Injectable Hormonal Contraceptives

Long-term use of depot medroxyprogesterone acetate (DMPA, brand name Depo-Provera) injections is linked to significant, though often reversible, bone loss.

• How they cause bone loss: The injection suppresses estrogen production, which is crucial for maintaining bone density. The manufacturer includes a black box warning about the risk.

Diuretics and Other Drugs

• Loop Diuretics: Medications like furosemide (Lasix) increase the excretion of calcium through the kidneys, which can negatively impact bone density over time, especially at high doses.
• Anticoagulants: Long-term, high-dose use of unfractionated heparin has been linked to bone loss. The impact of warfarin is controversial, but it can interfere with vitamin K, which is important for bone health.
• Excessive Thyroid Hormone: If hypothyroidism is overtreated, the excess hormone can speed up bone turnover, leading to more bone resorption than formation.
• Immunosuppressants: Cyclosporine and tacrolimus, used after organ transplants, are associated with increased bone loss and fracture risk.

How to Mitigate Medication-Induced Bone Loss

If you are on or starting one of these medications, it is vital to discuss bone health with your doctor. They can help you create a plan to mitigate the risks. This may include:

• Regular Monitoring: Your doctor may recommend a bone mineral density (BMD) test via dual-energy X-ray absorptiometry (DXA) scan to track your bone health.
• Nutritional Support: Ensure adequate intake of calcium and vitamin D through diet and/or supplementation. The recommended daily intake for most adults is 1,000–1,200 mg of calcium and 600–800 IU of vitamin D.
• Lifestyle Modifications: Engage in regular weight-bearing exercise, which stimulates bone growth. Limiting alcohol and quitting smoking are also highly beneficial.
• Medication Alternatives or Adjuncts: In some cases, your doctor may switch you to a different medication with a lower bone loss risk or prescribe an osteoporosis-specific medication, such as a bisphosphonate, to counteract the bone-weakening effects.

Medication Effects on Bone: A Comparison Table

Drug Class	Mechanism of Bone Loss	Reversibility on Discontinuation	Management Strategy	Risk Level
Glucocorticoids	Inhibits osteoblast activity, increases osteoclast activity, impairs calcium absorption.	Fracture risk declines, but may not return to baseline.	Monitor BMD, supplement calcium/vitamin D, may require bisphosphonates.	High
Aromatase Inhibitors	Reduces estrogen levels, which normally protect bone.	Incomplete recovery of BMD after discontinuation.	Monitor BMD, supplement calcium/vitamin D, may require bone-building therapy.	High
Antiepileptic Drugs (older)	Increases vitamin D metabolism, decreases calcium absorption.	Conflicting evidence, but some reversibility possible.	Monitor vitamin D levels, supplement calcium/vitamin D.	Moderate to High
Proton Pump Inhibitors	Reduces calcium absorption due to suppressed stomach acid.	Fracture risk reduces within a year of stopping.	Shorter-term use when possible, supplement calcium citrate.	Moderate (with long-term use)
SSRIs	Interfere with serotonin's role in bone metabolism; increase falls.	Variable; depends on duration and individual response.	Evaluate risk factors, consider dose changes, monitor bone density.	Moderate
DMPA (Depo-Provera)	Suppresses estrogen production.	Largely reversible, but may take time.	Limit duration, ensure adequate calcium and vitamin D intake.	Moderate (with long-term use)

Conclusion

While many medications are critical for managing serious health conditions, awareness of their potential side effects on bone health is essential. The link between certain drugs and bone loss is well-established, particularly for glucocorticoids, some cancer therapies, and PPIs. Proactive monitoring and management strategies, including discussing risks with a healthcare provider, ensuring sufficient calcium and vitamin D intake, and engaging in weight-bearing exercise, can significantly mitigate the risk of drug-induced osteoporosis and fractures. Patients should never stop a prescribed medication without first consulting their doctor to explore safe alternatives or protective measures. For additional authoritative information on osteoporosis, visit the International Osteoporosis Foundation website.

Outbound link: International Osteoporosis Foundation

Frequently Asked Questions

Can I stop taking a medication if I am worried about bone loss?

No, you should never stop a prescribed medication without first consulting your doctor. A healthcare professional can discuss alternative treatments, adjust your dosage, or prescribe other medications to protect your bone health while you continue necessary therapy.

How can I tell if my medication is causing bone loss?

Symptoms of bone loss often go unnoticed until a fracture occurs. The most accurate way to monitor your bone health is through a bone mineral density (BMD) test using a DXA scan, which your doctor may recommend if you are taking a high-risk medication.

Are all antidepressants bad for bones?

Not all antidepressants have the same effect. While chronic use of SSRIs has been linked to lower bone density and increased fracture risk, the mechanisms are complex, and the risk varies depending on the specific medication, dosage, and duration. Always discuss your concerns with your doctor.

What is the role of calcium and vitamin D in preventing medication-induced bone loss?

Calcium and vitamin D are essential for maintaining bone strength. Ensuring adequate intake through diet and supplementation can help counteract the negative effects of some medications that interfere with their absorption or metabolism. However, this may not be enough for all high-risk drugs.

Does short-term use of corticosteroids cause permanent bone loss?

Bone loss is most rapid during the first few months of oral corticosteroid use, but the risk and extent of loss are significantly higher with long-term therapy. The risk of fracture typically decreases after the medication is stopped, but may not fully return to baseline.

Can I prevent bone loss from PPIs?

To mitigate the risk from proton pump inhibitors, doctors may recommend using the lowest effective dose for the shortest duration necessary. If long-term use is unavoidable, supplementing with calcium citrate, which is more easily absorbed in a low-acid environment, may be beneficial.

Are there any medications that can strengthen bones while I am on another bone-damaging drug?

Yes, for patients on high-risk medications, such as corticosteroids, doctors can prescribe bisphosphonates (like alendronate) or other osteoporosis treatments to prevent bone loss and help maintain bone density.