Focus on Pharm: Bisphosphonates
A few weeks ago I wrote about osteoporosis, and one of the mainstays of treatment is a class of drugs called bisphosphonates. To learn what you need to know for exams and clinical, let’s go through bisphosphonates using the Straight A Nursing DRRUGS framework.
You can listen to the below information by tuning in to episode 215 of the Straight A Nursing podcast, available right from this website or wherever you get your podcast fix.
D: Drug Class
Bisphosphonates are a pharmacologic class of drugs used to treat disorders of the bone by inhibiting osteoclast activity. Recall from anatomy and physiology that osteoclasts are cells that break down bone. By inhibiting their formation and action, we inhibit the breakdown or resorption of bone and this leads to increased bone mineral density.
R: Routes of Administration
Bisphosphonate can be given PO and IV.
- Alendronate (Fosamax) – PO tablets, effervescent tablets and elixir
- Risedronate (Actonel) – PO immediate release and extended release
- Ibandronate (Boniva) – PO tablets and IV
- Pamidronate – IV
- Zoledronic acid – IV
R: Regular Dose Range
When looking at alendronate, the most commonly prescribed bisphosphonate, the standard dose ranges are:
- Osteoporosis prevention – 5 mg per day or 35 mg once per week
- Osteoporosis treatment – 10 mg per day or 70 mg once per week
U: Uses of bisphosphonates
The key use of bisphosphonates is in the treatment of bone disorders including osteoporosis, osteopenia, Paget’s disease, hypercalcemia secondary to malignancy, and the treatment of some cancers. For your exams, these medications are most likely to be utilized for osteoporosis. Let’s look at some of the key features of each one.
- Alendronate (Fosamax) – PO medication used to treat osteoporosis and to decrease progression of Paget’s disease. Studies show alendronate increases bone density more than risedronate.
- Risedronate (Actonel) – PO medication used to treat osteoporosis (including corticosteroid-induced osteoporosis) and Paget’s disease in men and women
- Ibandronate (Boniva) – PO and IV medication used to treat postmenopausal osteoporosis. Studies show it is specifically helpful for reducing vertebral fractures.
- Pamidronate (Aredia) – IV medication that may be used to treat osteoporosis in individuals who cannot tolerate oral bisphosphonates. It is also used to treat hypercalcemia and to prevent skeletal complications associated with breast cancer, prostate cancer and multiple myeloma.
- Zoledronic acid – Zometa is used in the treatment of malignancy-related hypercalcemia and for the treatment of multiple myeloma and bone metastases of solid tumors. Reclast is utilized for Paget’s disease, osteoporosis in men, osteoporosis in postmenopausal women and osteoporosis secondary to long-term glucocorticoid use. Both formulations are administered intravenously.
Additionally, you may see bisphosphonates used off-label for osteogenesis imperfecta in both pediatric and adult patients.
Oral bisphosphonates must be taken on an empty stomach in the morning in order to improve absorption. They must also be taken with a full glass of water to prevent the tablet from getting stuck in the esophagus, which can lead to esophageal irritation.
The patient should remain upright (sitting or standing) for 30-60 minutes after administration to ensure it does not remain in the esophagus. Additionally, in order to increase absorption, the individual should not eat, drink, or take other medications for 30-60 minutes.
Contraindications to bisphosphonate therapy include renal disease, hypocalcemia, esophagitis, pregnancy, breastfeeding, and gastric ulcers. Additionally, individuals who cannot sit upright for 30-60 minutes or who have difficulty swallowing will likely be prescribed an IV formulation rather than PO.
The patient should have a dental exam prior to treatment and periodically as these medications can cause osteonecrosis of the jaw, especially if they have a current oral infection or prior history of tooth extraction, malignancy, or jaw trauma. Additionally, serial bone scans are utilized to assess the patient’s response to bisphosphonate therapy.
Teach patients to take all necessary steps to promote healthy bones such as:
- Taking a calcium and Vit D supplement as advised by their MD or NP (note these should be taken at a different time of day than the bisphosphonate as calcium can affect absorption).
- Engaging in regular exercise such as walking or yoga
- Eating a diet rich in calcium with foods such as yogurt, spinach, broccoli and cottage cheese
And, of course, teach the patient the safe administration guidelines which include, taking the medication on an empty stomach in the morning, taking the medication with a full glass of water, staying upright for 30-60 minutes, and not ingesting any other meds, fluids or foods during that time.
S: Side Effects of bisphosphonates
One of the most worrisome side effects with bisphosphonates is esophageal irritation. This can range from esophagitis to erosion, ulceration and perforation of the esophagus. When the tablet sits against the mucosa of the esophagus, it compromises the protective lining of the mucosa which allows gastric acid to cause damage. This is why it is imperative that your patient take the medication with a full glass of water and remain upright for 30-60 minutes. Other GI adverse effects include nausea, indigestion, abdominal pain, flatulence and constipation.
Additionally, bisphosphonates commonly cause musculoskeletal pain and stiffness, fever, electrolyte deficiencies and even leukopenia.
Though not as common, bisphosphonates can cause osteonecrosis of the jaw which is why it is advised individuals get a thorough dental examination prior to initiating treatment and periodically throughout. And, while it may seem counterintuitive, these medications can lead to stress fractures of the femur. This is thought to be due to over-suppression of bone turnover or an impaired ability to repair bone in individuals who take bisphosphonates for many years.
I hope this helps you understand this interesting class of drugs for your nursing school exams. Interested in learning more about osteoporosis? You can read about it here or listen to the Straight A Nursing podcast episode here.
The information, including but not limited to, audio, video, text, and graphics contained on this website are for educational purposes only. No content on this website is intended to guide nursing practice and does not supersede any individual healthcare provider’s scope of practice or any nursing school curriculum. Additionally, no content on this website is intended to be a substitute for professional medical advice, diagnosis or treatment.
Amgen. (n.d.). What is EVENITY® (romosozumab-aqqg)? https://www.evenity.com/why-evenity/how-evenity-works
AngaeCal. (n.d.). What Causes Senile Osteoporosis (And How Can You Prevent It)? https://www.algaecal.com/expert-insights/causes-senile-osteoporosis-can-prevent/
Cannarella, R., Barbagallo, F., Condorelli, R. A., Aversa, A., La Vignera, S., & Calogero, A. E. (2019). Osteoporosis from an Endocrine Perspective: The Role of Hormonal Changes in the Elderly. Journal of Clinical Medicine, 8(10), 1564. https://doi.org/10.3390/jcm8101564
Cohen, O., Rais, T., Lepkifker, E., & Vered, I. (1998). Lithium carbonate therapy is not a risk factor for osteoporosis. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 30(9), 594–597. https://doi.org/10.1055/s-2007-978939
Davis Drug Guide. (n.d.). Denosumab. https://fadavispt.mhmedical.com/content.aspx?bookid=1873§ionid=139007531
Delitala, A. P., Scuteri, A., & Doria, C. (2020). Thyroid Hormone Diseases and Osteoporosis. Journal of Clinical Medicine, 9(4), 1034. https://doi.org/10.3390/jcm9041034
Do, H. J., Shin, J.-S., Lee, J., Lee, Y. J., Kim, M., Nam, D., Kim, E.-J., Park, Y., Suhr, K., & Ha, I.-H. (2018). Association between liver enzymes and bone mineral density in Koreans: A cross-sectional study. BMC Musculoskeletal Disorders, 19, 410. https://doi.org/10.1186/s12891-018-2322-1
Dobbs, M. B., Buckwalter, J., & Saltzman, C. (1999). Osteoporosis. The Iowa Orthopaedic Journal, 19, 43–52.
Evidence Based Medicine Consult. (n.d.). Bisphosphonates Mechanism of Esophageal and Gastrointestinal Irritation. https://www.ebmconsult.com/articles/what-is-the-mechanism-by-which-bisphosphonates-cause-esophageal-and-gastrointestinal-irritation
Hansdóttir, H. (2008). Raloxifene for older women: A review of the literature. Clinical Interventions in Aging, 3(1), 45–50.
Ito, T., & Jensen, R. T. (2010). Association of Long-term Proton Pump Inhibitor Therapy with Bone Fractures and effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium. Current Gastroenterology Reports, 12(6), 448–457. https://doi.org/10.1007/s11894-010-0141-0
Ji, M.-X., & Yu, Q. (2015). Primary osteoporosis in postmenopausal women. Chronic Diseases and Translational Medicine, 1(1), 9–13. https://doi.org/10.1016/j.cdtm.2015.02.006
Kroll, M. H. (2000). Parathyroid hormone temporal effects on bone formation and resorption. Bulletin of Mathematical Biology, 62(1), 163–188. https://doi.org/10.1006/bulm.1999.0146
Mayo Clinic. (n.d.-a). How osteoporosis is diagnosed. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/osteoporosis/in-depth/osteoporosis/art-20304599
Mayo Clinic. (n.d.-b). Osteoporosis—Diagnosis and treatment. https://www.mayoclinic.org/diseases-conditions/osteoporosis/diagnosis-treatment/drc-20351974
Mayo Clinic. (n.d.-c). Osteoporosis—Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/osteoporosis/symptoms-causes/syc-20351968
Mayo Clinic. (2021, July 20). Migraine—Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/migraine-headache/symptoms-causes/syc-20360201
Mohamad, N.-V., Soelaiman, I.-N., & Chin, K.-Y. (2016). A concise review of testosterone and bone health. Clinical Interventions in Aging, 11, 1317–1324. https://doi.org/10.2147/CIA.S115472
NCBI. (n.d.). The Basics of Bone in Health and Disease. https://www.ncbi.nlm.nih.gov/books/NBK45504/
Neuls, D. (n.d.). Why Stress is Harmful to Bone Health. Griswold Home Care. https://www.griswoldhomecare.com/blog/2019/august/why-stress-is-harmful-to-bone-health/
NIH. (n.d.). What Prostate Cancer Survivors Need To Know About Osteoporosis. https://www.bones.nih.gov/health-info/bone/osteoporosis/conditions-behaviors/osteoporosis-prostate-cancer
Ohio, D. H., RPh, PharmD Associate Professor of Family Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio Associate Clinical Professor of Pharmacy Practice, Ohio Northern University College of Pharmacy, Ada, Ohio Brittany Henak, RPh, PharmD Pharmacy Practice Resident Akron General Medical Center, Akron. (n.d.). Drug-Induced Osteoporosis. https://www.uspharmacist.com/article/drug-induced-osteoporosis
Osteoporosis. (n.d.). Cortisol and Bone Loss. Osteoporosis. https://mavendoctors.io/osteoporosis/bone-health/cortisol-and-bone-loss
Rosen, H. (n.d.). Bisphosphonate therapy for the treatment of osteoporosis—UpToDate. https://www.uptodate.com/contents/bisphosphonate-therapy-for-the-treatment-of-osteoporosis
Rosen, H., & Drezner, M. (n.d.-a). Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women—UpToDate. https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-evaluation-of-osteoporosis-in-postmenopausal-women?search=osteoporosis%20diagnosis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H9
Rosen, H., & Drezner, M. (n.d.-b). Menopausal hormone therapy in the prevention and treatment of osteoporosis. UpToDate. https://www.uptodate.com/contents/menopausal-hormone-therapy-in-the-prevention-and-treatment-of-osteoporosis#H2
Rosen, H., & Drezner, M. (n.d.-c). Overview of the management of osteoporosis in postmenopausal women—UpToDate. https://www.uptodate.com/contents/overview-of-the-management-of-osteoporosis-in-postmenopausal-women?search=osteoporosis%20treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
The North American Menopause Society. (n.d.). Bone Health at Menopause, Menopause Information & Articles. https://www.menopause.org/for-women/menopauseflashes/bone-health-and-heart-health/frax-sup-sup-a-tool-for-estimating-your-fracture-risk
UC San Diego Health. (n.d.). Osteoporosis Risk Factors. https://health.ucsd.edu/specialties/endocrinology/osteoporosis/Pages/osteoporosis-risk-factors.aspx
Woo, T. M., & Robinson, M. V. (2016). Pharmacotherapeutics for Advanced Practice Nurse Prescribers (Fourth Edition). F. A. Davis Company.
Zhao, W., Byrne, M. H., Boyce, B. F., & Krane, S. M. (1999). Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice. Journal of Clinical Investigation, 103(4), 517–524.