An Overview of the Benefits and Risks of Drugs Used to Treat Osteoporosis

Osteoporosis is a common condition characterized by weakened bones that are more prone to fractures. It affects millions of people worldwide, particularly women after menopause. While there are drugs available to treat osteoporosis that are commonly prescribed to help strengthen bones, they do come with risks. In addition, they do not treat the underlying causes of osteoporosis. In this blog, we will discuss the different types of drugs used to treat osteoporosis, their benefits, and potential adverse effects of long-term use.

1. Bisphosphonates: Bisphosphonates are the most commonly prescribed drugs for osteoporosis. They work by inhibiting the breakdown of bone tissue, helping to maintain bone density. Examples of bisphosphonates include Alendronate (Fosamax), Zoledronate (Zometa, Aclasta), Zoledonic Acid (Reclast), Risedronate (Actonel), Ibandronate (Boniva), Pamidronate (Aredia), Etidronate (Didronel), Tiludronate (Skelid), Neridronate (Nerixia), and Clodronate (Bonefos, Loron). These drugs have been shown to reduce the risk of fractures in people with osteoporosis.

Benefits: Bisphosphonates are effective in increasing bone density and reducing fracture risk. They are usually taken orally once a week or once a month, making them convenient for most patients.

Adverse effects: Long-term use of bisphosphonates has been associated with rare but serious side effects, such as osteonecrosis of the jaw, atypical fractures of the thigh bone, and unusual fractures of the hips.

Some patients may also experience gastrointestinal issues, such as nausea and heartburn, as well as esophageal erosion. In fact, stomach and esophageal irritation commonly lead to individuals electing to discontinue the drug. Some of this can be avoided by following appropriate medication dosing directions.

Other side effects include flu-like symptoms, increased risk of atrial fibrillation (especially with intravenous versus oral administration), fatigue, decreased strength, decreased kidney function, eye inflammation, poor healing of bone fractures, and increased risk of fracture. The side effects vary among bisphosphonates and route of administration.

2. Hormone therapy: Hormone therapy, specifically estrogen replacement therapy, has been used to help prevent osteoporosis in postmenopausal women. However, it is not a first-line treatment for osteoporosis and is generally recommended for women with postmenopausal symptoms or under the age of 60.

Benefits: Estrogen replacement therapy can help prevent bone loss and reduce the risk of fractures in postmenopausal women. It reduces the risk of hip, vertebral, and all fractures by approximately 20–40%. It also has the added benefit of relieving menopausal symptoms, such as hot flashes and vaginal dryness.

Adverse effects: The risks of hormone therapy, including an increased risk of breast cancer, heart disease, and stroke, must be carefully weighed against the benefits of treatment. Hormone therapy is usually not recommended for long-term use in women with osteoporosis.

3. Denosumab: Denosumab (Prolia) is a newer type of drug used to treat osteoporosis. It works by inhibiting a protein that promotes bone breakdown. Denosumab is administered as an injection every six months and has been shown to increase bone density and reduce the risk of fractures in postmenopausal women with osteoporosis.

Benefits: Denosumab is effective in increasing bone density and reducing fracture risk. It is generally well-tolerated and does not have the same gastrointestinal side effects as bisphosphonates.

Adverse effects: Long-term denosumab use has been associated with an increased risk of infections and skin reactions. There is also a potential risk of developing hypocalcemia, a condition where the calcium levels in the blood are too low. Atypical hip fractures, or osteonecrosis of the jaw, may also occur. It should be given with caution to individuals with compromised kidney function, with careful monitoring of calcium levels along with supplementation of vitamin D and calcium as indicated.

Unfortunately, discontinuing treatment is associated with a severe rebound effect including a sharp increase in bone turnover markers, loss of the bone density gained, and a risk of nearly 20% of multiple vertebral fractures in postmenopausal women.

In conclusion, while there are drugs available to treat osteoporosis, each comes with its own benefits and risks. It is important for patients to discuss their treatment options with their healthcare provider and weigh the potential benefits against the risks of long-term use. While these drugs may help strengthen bones and reduce the risk of fractures, it is important to be aware of potential adverse effects and downsides of treatment. A holistic approach can help to address underlying causes of bone loss. By working closely with their healthcare team, patients can effectively manage their osteoporosis and maintain bone health.

To learn more about potential underlying causes of osteoporosis and natural ways to support bone health even if using medications, click below for a free discovery call.

References:

Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC. Bisphosphonates and risk of cardiovascular events: a meta-analysis. PLoS One. 2015 Apr 17;10(4):e0122646. doi: 10.1371/journal.pone.0122646. PMID: 25884398; PMCID: PMC4401508.

Black DM, Geiger EJ, Eastell R, Vittinghoff E, Li BH, Ryan DS, Dell RM, Adams AL. Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. N Engl J Med. 2020 Aug 20;383(8):743-753. doi: 10.1056/NEJMoa1916525. PMID: 32813950; PMCID: PMC9632334.

Sharma A, Chatterjee S, Arbab-Zadeh A, Goyal S, Lichstein E, Ghosh J, Aikat S. Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis. Chest. 2013 Oct;144(4):1311-1322. doi: 10.1378/chest.13-0675. PMID: 23722644.

Lanza FL. Gastrointestinal adverse effects of bisphosphonates: etiology, incidence and prevention. Treat Endocrinol. 2002;1(1):37-43. doi: 10.2165/00024677-200201010-00004. Erratum in: Treat Endocrinol. 2002;1(4):210. PMID: 15765619.

Tadrous M, Wong L, Mamdani MM, Juurlink DN, Krahn MD, Lévesque LE, Cadarette SM. Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis. Osteoporos Int. 2014 Apr;25(4):1225-35. doi: 10.1007/s00198-013-2576-2. Epub 2013 Nov 28. PMID: 24287510.

Chartrand NA, Lau CK, Parsons MT, Handlon JJ, Ronquillo YC, Hoopes PC, Moshirfar M. Ocular Side Effects of Bisphosphonates: A Review of Literature. J Ocul Pharmacol Ther. 2023 Jan-Feb;39(1):3-16. doi: 10.1089/jop.2022.0094. Epub 2022 Nov 21. PMID: 36409537.

Rozenberg S, Al-Daghri N, Aubertin-Leheudre M, Brandi ML, Cano A, Collins P, Cooper C, Genazzani AR, Hillard T, Kanis JA, Kaufman JM, Lambrinoudaki I, Laslop A, McCloskey E, Palacios S, Prieto-Alhambra D, Reginster JY, Rizzoli R, Rosano G, Trémollieres F, Harvey NC. Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis? Osteoporos Int. 2020 Dec;31(12):2271-2286. doi: 10.1007/s00198-020-05497-8. Epub 2020 Jul 8. PMID: 32642851; PMCID: PMC7661391.

Sánchez A, Brun LR, Salerni H, Costanzo PR, González D, Bagur A, Oliveri B, Zanchetta MB, Farías V, Maffei L, Premrou V, Mansur JL, Larroudé MS, Sarli MA, Rey P, Ulla MR, Pavlove MM, Karlsbrum S, Brance ML. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis. J Osteoporos. 2016;2016:8738959. doi: 10.1155/2016/8738959. Epub 2016 Aug 8. PMID: 27579211; PMCID: PMC4992763.

Lamy O, Everts-Graber J, Gonzalez Rodriguez E. Denosumab for osteoporosis treatment: when, how, for whom, and for how long. A pragmatical approach. Aging Clin Exp Res. 2025 Mar 8;37(1):70. doi: 10.1007/s40520-025-02991-z. PMID: 40055268; PMCID: PMC11889064.

Gopaul A, Kanagalingam T, Thain J, Khan T, Cowan A, Sultan N, Clemens KK. Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety. Arch Osteoporos. 2021 Jul 28;16(1):116. doi: 10.1007/s11657-021-00971-0. PMID: 34319515.