Osteoporosis: Making Sense of a Diagnosis and Tough Decisions About Treatment

Article taken from pages 6-7 of January/February Newsletter 2018

By Caila Brander

So, you just got home from the doctor with your DEXA bone density results in hand. You were told you have osteoporosis. Should you start taking medication? Are there things you can do without medication? What information can you trust?

Each year, thousands of women are diagnosed with osteoporosis, a condition of weak and brittle bones that’s completely painless until it leads to a bone fracture. An even larger number of women will be told they have osteopenia, a supposed “precursor” condition to osteoporosis in which a person’s bones are weaker than a young woman with peak bone mass. The National Women’s Health Network (NWHN) has been a leader in spotlighting the lack of evidence for prescribing medication to women diagnosed with osteopenia, and we urge women to be very cautious about taking osteoporosis drugs solely on the basis of an osteopenia DEXA test result.  There are certainly cases where medication treatment is justified for women diagnosed with osteoporosis. How can you figure out which medication treatment is right for you?

Osteoporosis can be a scary diagnosis, invoking images of hunched-over backs and painful hip fractures. The NWHN believes women deserve comprehensive, accurate information when making medical decisions. We do not accept financial support from drug and device manufacturers, so the information we provide is based purely on careful analyses of existing data and evidence. This article describes each category of drugs to treat osteoporosis that the Food and Drug Administration (FDA) has approved, including their risk, benefits, and what clinical experts recommend. We also describe ways to reduce your fracture risk without taking any medication. Armed with this comprehensive information, we hope you will feel empowered to speak with your health care provider and make treatment decisions that are right for you. (For more information on screening and diagnosis, see: https://nwhn.org/better-screening-treatment/.)

First-line Treatments for Osteoporosis

Bisphosphonates

Bisphosphonates work by stopping the activity of the cells that break down bone, called osteoclasts. Alendronate (Fosomax), etidronate (Didronel) and zoledronic acid (Zometa) are the three most commonly-prescribed bisphosphonates. Studies have shown these medications are effective at boosting bone density and preventing a second fracture after a woman has experienced a fracture once before (called a secondary fracture). These bisphosphonates have not yet demonstrated in clinical trials, however, that they can prevent a first-time fracture.[1]

Bisphosphonates can be administered either by pill or intravenously; most people take them in pill form. The pill has particular instructions for safe use: a person cannot lay down, consume food, or take any other medication for 30 minutes after taking the pill, because the pills can linger in the throat and have corrosive, carcinogenic effects.[2]

Roughly a decade after these drugs came to market, the FDA began receiving reports of rare but serious complications like disintegration of the jaw (called osteonecrosis of the jaw) and painful thighbone fractures that often occur spontaneously, without trauma (called atypical femur fractures).[3] The FDA reviewed these complaints and updated the drugs’ label with warnings about these dangerous complications.[4] At the time the complaints were being reported, bisphosphonates were being prescribed preventatively, meaning they were given to healthy women at low fracture risk. Now that bisphosphonates’ long-term risks are known, many clinical experts recommend they be used only to treat—not prevent —osteoporosis. Experts also recommend that bisphosphonates be used for a maximum of five years rather than indefinitely.[5]

The NWHN advises that women taking bisphosphonates immediately report any thigh pain to their doctor, as this may be a precursor to atypical femur fractures. Additionally, avoid having jaw surgery while taking bisphosphonates, as it can increase the likelihood of osteonecrosis of the jaw.

Bisphosphonates are often a first-line medication treatment for osteoporosis because they are affordable and do not require an injection. When women are fully informed about bisphosphonates’ potential side effects and how to detect warning signs, they can be a way to re-build bone density and reduce the risk of a second fracture.[6]

Monoclonal Antibodies

Monoclonal antibodies are used to inactivate osteoclasts. This drug is administered by injection just below the skin (e.g., subcutaneously) into the abdomen. Denosumab (Prolia) has been shown to build bone density and protect against vertebral, nonvertebral, and hip fractures. There are several serious health risks associated with denosumab, however. Its cellular targeting of the bone also causes denosumab to interact with the immune system, and possibly inactivate the person’s natural immune response. This became a concern when women who were in clinical trials and taking denosumab suffered serious infections requiring hospitalization at a higher rate than women taking placebo.[7] Denosumab has been shown to cause some of the same serious side effects that bisphosphonates do, including osteonecrosis of the jaw.[8] And, some evidence suggests it can cause painful atypical femur fractures.[9] For women at high fracture risk, denosumab may be worth it; much older women and women with weaker immune systems should seriously consider the balance of risks and benefits.

Denosumab is often recommended as a first-line treatment for women deemed to be at high fracture risk. Yet, the medication is very expensive and is not always covered by insurance. Bisphosphonates, which are much cheaper, could be an alternative option for women whose insurance does not cover denosumab.[10]

Treat with Caution! Other Treatments for Osteoporosis

Peptide Hormones

Another category of treatment medication includes drugs modeled after the hormones in our bodies that stimulate osteoblasts, the bone cells that produce more bone mass. These drugs have synthetic hormone fragments, called peptides, which mimic the effects of the body’s real hormones, thereby spurring osteoblasts to create more bone tissue. Two of these peptide hormone medications are abaloparatide (brand name Tymlos) and teriparatide (brand name Forteo). Abaloparatide is laboratory-made copy of part of the parathyroid hormone-related protein (PTHrP); teriparatide is a partial copy of parathyroid hormone. They are administered through an injection into the fatty tissue of the woman’s thigh or abdomen. (Calcitonin,brand name Miacalcin) is a synthetic peptide of the calcitonin hormone that has been approved to treat osteoporosis. It is now considered obsolete, however, due to safety concerns and low efficacy compared to other treatments.[11])

These treatments have been shown to reduce vertebral fractures and increase bone density in the hip and spine, but only slightly.[12] These treatments are not as effective at reducing fractures when compared to other FDA-approved treatments, like bisphosphonates and monoclonal antibodies. They also have serious safety concerns. During pre-human trails, when the drug was being studied in rats, teriparatide caused a type of malignant bone cancer called osteosarcoma; as a result, these drugs carry a “Black Box” safety warning about their risk of causing bone cancer if used for longer than two years.[13] Because of these safety concerns and the drugs’ lower efficacy at preventing fractures, peptide hormones are considered to be second-line treatment for osteoporosis. They are only approved for patients who have serious osteoporosis, classified by the FDA as individuals who have a history of osteoporotic fracture, have multiple risk factors for fracture, or have exhausted all other available osteoporosis treatments.[14]

Menopause Hormones & SERMs

Menopause hormone therapy — either combined estrogen and progesterone, or estrogen alone — was commonly prescribed to alleviate symptoms of the menopausal transition and reduce the risk of osteoporosis. While menopause hormone therapy does increase bone density and reduce fracture risk, the drugs can cause serious health problems. Specifically, menopause hormone therapy has been shown to increase women’s risk of breast cancer, blood clots, heart attack, and stroke.[15] As a result, clinical guidelines now recommend against using menopause hormone therapy for osteoporosis.

Selective estrogen receptor modulators (SERMs) like raloxifene (brand name Evista) build bone density in the same way that estrogen does, while having an anti-estrogen effect on other tissues. SERMs have been shown to reduce vertebral fractures, but have no impact on the risk of hip fractures. They also increase the risk of life-threatening blood clots.[16] Due to SERMs’ marginal impact on reducing fracture compared with their risks, clinical guidelines no longer recommend their use for osteoporosis treatment, unless a patient is unable to tolerate other treatments.[17]

Non-Pharmacologic Interventions to Reduce Fractures

Falls cause more than 95 percent of hip fractures, which are arguably the most debilitating type of fracture associated with osteoporosis.[18] If you have osteoporosis, there are several ways to reduce your risk of falling and experiencing a fracture without taking any pills or injections. Making your home “fracture-proof” is an excellent place to start. Studies show that the risk of fracture can be successfully reduced by taking precautions like taping down the edges of rugs and mats, installing textured pads in showers and on slippery floors, ensuring your home has good lighting (especially in stairways), and wearing stable nonslip shoes around the house.[19] Whenever you leave your house, wear nonslip shoes and be aware of, and cautious on, slippery surfaces, especially in the winter when walkways can be icy.

Engaging in consistent exercise, especially daily balance training, can help strengthen muscles that stabilize the body.[20] Balance training exercises can be found online and can be done at home. Classes and programs also exist, and may be advisable for those who are more frail. Because poor vision can lead to tripping and/or slipping, and possibly to fractures, getting regular vision checks and using prescription eyewear are also important. If you wear bi- or trifocal glasses, exercise with your eyewear on to ensure that you don’t fall while exercising.

Check your prescription drug side effects. Many drugs prescribed to older adults can cause dizziness or fainting, which can cause falls and possibly fractures. Learn more about your drugs’ the side effects by checking the FDA label either online or in the package. It’s good practice to schedule an annual appointment with your primary care physician to review your current medications; these are called “brown bag” appointments, when patients put all of their medications into a bag and bring them in for their provider to review. This may help you avoid taking unnecessary medications that cause dizziness or fainting. If you cannot avoid taking medications that cause dizziness or fainting, you can prevent falls by taking precautions like sitting down whenever you feel dizzy.

Conclusion

Deciding whether or not to start taking medication is never easy. Neither is sifting through information on each drug, weighing your options, and figuring out what treatment is likely to work best for you. It is helpful to weigh the side effects of each treatment not only against each other, but also against the risk of experiencing a painful or debilitating fracture. This will help you decide which risk you will be most comfortable with. With comprehensive information at your disposal, the decision is yours to make.

 

Caila Brander was the NWHN Policy Fellow in 2017. She is currently a Program Assistant for Health IT and Clinical Informatics at the American College of Obstetricians and Gynecologists

References

[1] Wells GA, Cranney A, Peterson J, et al. “Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women,” Cochrane Database of Systematic Reviews 2008; Wells GA, Cranney A, Peterson J, et al., “Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women,” Cochrane Database of Systematic Reviews 2008 (1); Wells GA, Cranney A, Peterson J, et al., “Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women,” Cochrane Database of Systematic Reviews 2008 (1).

[2] Wysowski DK, “Reports of Esophageal Cancer with Oral Bisphosphonates” N Engl J Med 2009; 360:98-90.

[3] Dell RM, Adams AL, Greene DF, et al., “Incidence of atypical nontraumatic diaphyseal

fractures of the femur,” J Bone Miner Res 2012;27:2544-50.

[4] U.S. Food and Drug Administration (FDA), FDA Drug Safety Communication: Safety updates for osteoporosis drugs, bisphosphonates, and atypical fractures, Rockville (MD): FDA, August 3, 2017. Online: https://www.fda.gov/Drugs/DrugSafety/ucm229009.htm.

[5] Schilcher J, Michaelsson K, Aspenberg P, “Bisphosphonate use and atypical fractures of

the femoral shaft,” N Engl J Med 2011;364:1728-37.

[6] McClung MR, Wasnich RD, Hosking DJ, et al., “Prevention of Postmenopausal Bone Loss: Six-Year Results from the Early Postmenopausal Intervention Cohort Study,” The Journal of Clinical Endocrinology & Metabolism 2004; 89(10): 4879–4885. Online: https://doi.org/10.1210/jc.2003-031672.

[7] Watts N, Roux C, Modlin J, et al., “Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?” Osteoporos Int. 2012;23(1):327–37.

[8] Geller G, Wagman R, Ho P, et al., “Early findings from Prolia post-marketing safety surveillance for atypical femoral fracture, osteonecrosis of the jaw, severe symptomatic hypocalcemia, and anaphylaxis,” Ann Rheumatic Disease 2014; 73:766-7.

[9] Drampalos E, Skarpas G, Barbounakis N, Michos I, “Atypical femoral fractures bilaterally in a patient receiving denosumab,” Acta Orthop 2014; 85(1)3-5.

[10] Johnson G, “Denosumab (Prolia) for treatment of postmenopausal osteoporosis,” Am Fam Physician 2012; 85(4):334-6.

[11] Qaseem A, Forciea MA, McLean RM, et al., “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians,” Ann Intern Med. 2017;166(11):818-39.

[12] Trevisani VF, Riera R, Imoto AM, et al., “Teriparatide (recombinant human parathyroid hormone 1-34) in postmenopausal women with osteoporosis: systematic review,” Sao Paulo Med J. 2008;126(5):279-84.

[13] Forteo [package insert]. Eli Lilly and Company. 2002. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021318s012lbl.pdf

[14] Ibid.

[15] U.S. Preventative Service Task Force (USPSTF), Final Recommendation Statement: Menopause Hormone Therapy: Preventative Medication, Rockville (MD): USPSTF, October 2012. Online: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/menopausal-hormone-therapy-preventive-medication.

[16] Qaseem A, Forciea MA, McLean RM, et al., “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians,” Ann Intern Med. 2017;166(11):818-39.

[17] Ibid.

[18] Parkkari J, Kannus P, Palvanen M, et al., “Majority of Hip Fractures Occur as a result of a fall and impact on the greater trochanter of the femur: A prospective controlled hip fracture study with 206 consecutive patients,” Calcif Tissue Int. 1999;65:183-7.

[19] Centers for Disease Control and Prevention (CDC), Hip Fractures Among Older Adults, Atlanta (GA): CDC, 2016. Online: https://www.cdc.gov/homeandrecreationalsafety/falls/adulthipfx.html.

[20] Gillespie LD, Robertson MC, Gillespie WJ, et al., “Interventions for preventing falls in older people living in the community,” Cochran Database of Systematic Reviews 2012(9).