What drugs are associated with bone loss?: A pharmacological review

October 12, 2025 •

6 min read

According to the U.S. Pharmacist, drug-induced osteoporosis is a highly preventable condition, yet many physicians are unaware of the risk many common medications pose to bone health. This comprehensive guide explores what drugs are associated with bone loss, reviewing specific medication classes and their impact on skeletal integrity.

Quick Summary

This review covers medication classes known to cause reduced bone mineral density and increased fracture risk, including corticosteroids, PPIs, and certain contraceptives, often with long-term use.

Key Points

Glucocorticoids are a major cause: Long-term use of corticosteroids like prednisone significantly increases the risk of bone loss and fractures, especially in the first year of treatment.
PPIs affect bone over time: Proton pump inhibitors (e.g., omeprazole) are associated with a modest increase in fracture risk with prolonged use (over one year), potentially due to reduced calcium absorption.
Anticonvulsants can alter vitamin D metabolism: Certain anti-seizure medications, particularly older types, can accelerate vitamin D breakdown, leading to impaired calcium absorption and increased bone turnover.
Hormone-related treatments impact bone: Therapies for breast and prostate cancer, like aromatase inhibitors and androgen deprivation therapy, can cause bone loss due to reduced sex hormone levels.
DMPA-induced bone loss is largely reversible: While the injectable contraceptive Depo-Provera causes temporary bone mineral density loss, especially in younger women, this effect is largely reversible upon discontinuation.
Consult your doctor: Patients on long-term medications associated with bone loss should consult their healthcare provider for monitoring and preventative measures, including adequate calcium and vitamin D intake.

The impact of medication on bone health

Bone is a living tissue that undergoes continuous remodeling, a process where old bone is broken down by cells called osteoclasts and new bone is formed by osteoblasts. This delicate balance maintains bone strength and mass throughout life. Certain medications can disrupt this process, leading to accelerated bone resorption (breakdown) or impaired bone formation, which results in reduced bone mineral density (BMD) and an increased risk of fracture. This condition is known as drug-induced osteoporosis and is a significant health concern for patients on long-term therapy.

Glucocorticoids (Corticosteroids)

Glucocorticoids, such as prednisone and dexamethasone, are one of the most common causes of drug-induced bone loss. These powerful anti-inflammatory and immunosuppressive agents are used to treat a wide variety of conditions, including asthma, autoimmune diseases, and post-organ transplant.

Mechanism: Glucocorticoids impair bone health through multiple pathways. They directly decrease the number and activity of osteoblasts, the bone-forming cells, while increasing the lifespan of osteoclasts, the bone-resorbing cells. This leads to a net loss of bone mass. Additionally, they reduce the intestinal absorption of calcium and increase its excretion by the kidneys, further depleting the body's mineral reserves and leading to secondary hyperparathyroidism.
Risk Factors: The risk of bone loss is dose-dependent and increases significantly with long-term use (typically defined as more than 3 months). The rate of bone loss is most rapid in the first 6 to 12 months of therapy.
Management: Healthcare providers often recommend a baseline bone density measurement for patients starting long-term glucocorticoid therapy. Calcium and vitamin D supplementation are standard practice, and some patients may require additional medication, such as bisphosphonates, to protect bone health.

Proton pump inhibitors (PPIs)

Commonly used to treat acid reflux and ulcers, PPIs like omeprazole and lansoprazole have been linked to a modest increase in the risk of hip, wrist, and spine fractures, especially with long-term use (over one year) or high doses.

Mechanism: The exact mechanism is not fully understood, but one theory suggests that by reducing stomach acid, PPIs may decrease the intestinal absorption of calcium, a key mineral for bone strength. Another proposed mechanism involves PPIs inhibiting vacuolar-type ATPase (V-ATPase) in osteoclasts, which could affect bone turnover.
Risk Factors: The risk appears to be highest in older individuals and those using high-dose or long-term prescription PPIs. The FDA has issued safety communications regarding the potential increased fracture risk.
Management: For patients on long-term PPIs, healthcare providers should assess the need for continued use and ensure adequate calcium and vitamin D intake.

Anticonvulsants (Anti-seizure drugs)

Several antiepileptic drugs (AEDs) are associated with reduced bone mineral density and increased fracture risk. Older, enzyme-inducing AEDs like phenytoin, phenobarbital, and carbamazepine carry a higher risk.

Mechanism: Enzyme-inducing AEDs can accelerate the metabolism of vitamin D in the liver, leading to reduced levels of active vitamin D and, consequently, decreased calcium absorption from the gut. This can result in secondary hyperparathyroidism, which promotes bone resorption. Some AEDs may also have direct effects on bone-forming cells.
Risk Factors: The risk is higher with older-generation AEDs and increases with the duration of therapy. Patients may also experience a higher risk of falls, a significant contributor to fracture.
Management: Regular monitoring of vitamin D levels and bone density is often recommended for patients on long-term AEDs, along with calcium and vitamin D supplementation.

Hormone-related therapies

Aromatase Inhibitors (AIs): Used to treat hormone-receptor-positive breast cancer in postmenopausal women, AIs like anastrozole and letrozole work by blocking the production of estrogen. The resulting estrogen deficiency can lead to significant bone loss, increasing fracture risk.
Androgen Deprivation Therapy (ADT): This therapy for prostate cancer involves reducing male sex hormones, which can cause significant bone mineral density reduction and increased fracture risk in men.
Depot Medroxyprogesterone Acetate (DMPA): This injectable contraceptive (Depo-Provera) has been shown to cause a reversible decrease in bone mineral density, particularly with longer use. The bone loss is largely reversible after discontinuation, but concerns remain for adolescents whose peak bone mass is still developing.

Comparison of common drug classes causing bone loss


Drug Class	Primary Mechanism	Primary Risk Factor	Reversibility	Monitoring & Prevention	Fracture Risk (relative)
Glucocorticoids	Impaired bone formation, increased resorption, reduced calcium absorption	High dose, long-term use (>3 months)	Partial after discontinuation	Baseline DEXA, calcium, vitamin D, bisphosphonates	Higher, especially vertebral fractures
PPIs	Reduced calcium absorption (possible), potential effect on osteoclasts	Long-term use (>1 year), high dose	Risk may decline after stopping	Assess need for continued use, calcium, vitamin D	Modest increase (10-40%)
Anticonvulsants	Altered vitamin D metabolism, reduced calcium absorption	Older AEDs, long-term use	Variable, may be reversible	Vitamin D levels, calcium, vitamin D supplementation	Higher, especially with enzyme-inducing AEDs
Aromatase Inhibitors	Estrogen deprivation	Therapy duration in postmenopausal women	Partial recovery	Baseline DEXA, calcium, vitamin D, bisphosphonates	Increased risk of nonvertebral and vertebral fractures
DMPA	Estrogen suppression	Longer continuous use, especially in adolescents	Largely reversible	Encourage weight-bearing exercise, calcium, vitamin D	Uncertain, observational studies suggest possible risk

Other medications associated with bone effects

Anticoagulants: Long-term, high-dose unfractionated heparin has been linked to bone loss. The effects of warfarin are debated, but it can interfere with vitamin K, which is essential for bone protein formation.
Diuretics: Loop diuretics (e.g., furosemide) increase calcium excretion in the urine, potentially leading to bone loss. Conversely, thiazide diuretics are known to retain calcium and may have a protective effect.
Antidepressants: Some studies suggest that long-term use of selective serotonin reuptake inhibitors (SSRIs) may be associated with decreased bone density and an increased risk of fracture. This could be related to central or peripheral serotonin effects on bone cells.
Immunosuppressants: Calcineurin inhibitors like cyclosporine and tacrolimus, used for organ transplant and autoimmune disorders, are associated with bone loss.
Chemotherapy: Certain chemotherapeutic agents can cause osteoporosis, both directly and indirectly (e.g., through premature menopause in women).
Excess Thyroid Hormone: Overtreatment with thyroid hormone replacement, leading to undetectable TSH levels, can cause demineralization of bone.
Certain Diabetes Medications: Some type 2 diabetes medications, including thiazolidinediones like pioglitazone, have been associated with an increased risk of fracture.

Conclusion

Awareness of the risk factors for drug-induced osteoporosis is crucial for effective prevention and management. While many medications are vital for treating chronic and serious conditions, understanding their potential impact on bone health allows for proactive measures. Patients on long-term therapy, particularly with corticosteroids, PPIs, or certain anticonvulsants, should discuss bone health monitoring with their doctor. Lifestyle interventions, such as adequate calcium and vitamin D intake, regular weight-bearing exercise, and limiting alcohol and smoking, are important strategies for protecting bone mass. In some cases, specific medications like bisphosphonates may be necessary to counteract bone loss. Ultimately, working with a healthcare provider is the best approach to balance the benefits of necessary medications with the long-term health of your skeletal system.

For more information on bone health, visit the National Institutes of Health (NIH) at https://www.nih.gov/.

Potential interactions between medications and bone health

Lifestyle modifications and alternative treatments

Beyond pharmacological interventions, lifestyle changes, such as a balanced diet rich in calcium and vitamin D, regular exercise, and avoiding smoking and excessive alcohol, are foundational for preventing drug-induced bone loss. For some conditions, alternative medications with a lower risk profile may be considered after a careful risk-benefit analysis with a healthcare provider.

Bone health monitoring and screening

For individuals at high risk for drug-induced bone loss, a Dual-Energy X-ray Absorptiometry (DEXA) scan is a key diagnostic tool to measure bone mineral density. The World Health Organization's FRAX tool can also help calculate the 10-year probability of fracture. Regular monitoring allows for early detection and intervention to mitigate bone loss. Ultimately, the best strategy for managing drug-induced bone loss involves a combination of medication management, nutritional support, and lifestyle changes under the guidance of a healthcare professional.

Frequently Asked Questions

The most commonly cited medications associated with significant bone loss include glucocorticoids (corticosteroids) like prednisone, proton pump inhibitors (PPIs), some anticonvulsants (e.g., phenytoin), and hormone-related therapies for cancer.

Corticosteroids cause bone loss by decreasing the formation of new bone, increasing the rate of bone breakdown, and impairing the body's absorption of calcium from the gut, leading to a net loss of bone mass.

In some cases, yes. The bone loss caused by Depo-Provera is largely reversible after stopping the medication. With corticosteroids, the rate of bone loss slows after discontinuation, but recovery may be only partial.

No. You should never stop taking a prescribed medication without first speaking with your healthcare provider. The benefits of your medication may outweigh the risks, and your doctor can recommend strategies to protect your bone health while continuing treatment.

While adequate intake of calcium and vitamin D is essential for bone health, it may not be enough to prevent bone loss caused by certain medications, especially with high doses or long-term use. A doctor may recommend additional medications, such as bisphosphonates, to manage the risk.

A DEXA scan is a type of imaging test that measures bone mineral density. It is recommended for individuals at high risk of drug-induced osteoporosis, such as those on long-term corticosteroids, to assess bone health and guide management decisions.

Yes. Bisphosphonates, such as alendronate, are often used to treat drug-induced osteoporosis by slowing down the bone resorption process. In some cases, other medications like parathyroid hormone analogues may also be considered.