There are several categories of drugs being prescribed in the name of bone protection. In this article we discuss findings on the group known as bisphosphonates.

You’ve probably seen advertisements everywhere featuring a popular celebrity who warns you about bone loss right before endorsing a certain prescription drug.

While these ads may help somewhat in increasing our awareness about the importance of bone health, I so wish I had as much money as the big pharmaceutical companies in order to loudly broadcast the one message you should hear: you probably don’t really need a drug for healthy bones.

Possible adverse side effects associated with osteoporosis medications (bisphosphonates)
  • Ulcers of the esophagus
  • Upper GI irritation
  • Irregular heartbeat
  • Fractures of the femur
  • Low calcium in the blood
  • Skin rash
  • Joint, bone, and muscle pain
  • Jaw bone decay (osteonecrosis) (rare)
  • Increased parathyroid hormone (PTH)

My reasoning is based on my research and experience which both show the most popular forms of prescription medication — bisphosphonates (with the brand names Fosamax, Actonel, or Boniva) — are not the best way to prevent osteoporosis and fracture, may even hurt bone after continued use, and carry the risk of dangerous side effects.

As your bone health advocate, I encourage you to look carefully at any drug so you can make an informed decision about your personal treatment.

Take the Surgeon General’s advice — work with nature to protect bone health

If you are concerned about your bone health, I’m not the only one urging you to question the use of bisphosphonates as your first step. In 2004, the Surgeon General provided the following pyramid as guidance for protecting bone health:

  1. At the base (or what should be tried first): Prevention and treatment that starts with nutrition, physical activity, and fall prevention.
  2. The second tier involves assessing and treating the underlying causes of compromised bone health.
  3. The very tip of the pyramid, and the last resort, is pharmacotherapy — use of bone drugs.
Protect bone health

Unfortunately, many practitioners have turned this pyramid on its head, and prescribe bone drugs before trying anything else. It may seem easy to simply pop a pill and forget about it, but prescription medication is rarely easy on your body.

How bisphosphonates are supposed to work

Your practitioner may recommend a bisphosphonate based on the drug’s design to slow or stop the loss of bone density. The molecules of the drug attach themselves to the mineral surfaces in both cortical (outer compact bone) and trabecular (inner spongy matrix) bone to give an apparent increase in bone mass and a strengthening effect. It does this by preventing perforations that can weaken bone structure, as well as by interfering with cells that break down old bone — known as osteoclasts. This means resorption, the natural process of clearing out old bone, is inhibited, so that existing bone stays put for much longer periods than usual.

However... we know that there is a lag time during the first six to 12 months after starting the drugs, when the bone continues to build and stops being broken down. This initial uncoupling of the natural bone turnover process explains why results on bone density testing appear dramatic in the first year on a bisphosphonate.

But after a year, things start to change...

Bisphosphonates stop bone formation

Research shows that after the first year, markers for bone turnover — growth and resorption — go down dramatically . So bone is neither building up nor breaking down once you’ve been taking a bisphosphonate for more than a year or so.

While women who take bisphosphonates may appear to have denser bone initially on a bone scan, it doesn’t mean the bone is actually stronger. In fact, we know that bone naturally becomes less dense as we age, but what protects us from debilitating fracture is our inborn ability to repair, meaning to break down old bone and rebuild new bone naturally as part of a cycle.

And because this natural bone repair process is halted by drugs, it is very likely that long-term use will weaken, not strengthen, bone.

Dense bones may be brittle

FDA warns about bisphosphonate safety

On Oct. 23, 2010, the Food and Drug Administration (FDA) issued a public safety notice to both patients and healthcare providers warning “there is a possible risk of a rare type of thigh bone (femoral) fracture in people who take drugs known as bisphosphonates to treat osteoporosis.” The FDA also required a labeling change noting the risk.

I had a patient who had been on Fosamax for four years, then turned in her bedroom one evening and fell to the floor, breaking her leg in two separate places.

Though these “low-trauma” and “nontraumatic” fractures aren’t happening to large numbers of women on bisphosphonates, they certainly serve as a warning for those considering prolonged use of these drugs as “preventive medicine.” It also points to the fact that halting bone resorption doesn’t automatically give us stronger bones, and may in fact make them more brittle over time.

Spinning the numbers on bone health

What’s disappointing to me is the way numbers from studies can be manipulated to exaggerate treatment benefits. Statistical calculations are often complex and can be presented in many different ways — depending on what you want to say!

One way to “spin the numbers” is to present the results for specifically-selected study participants as representative of results for everyone else. In one study, researchers asked if “real-world” patients taking bone drugs received the same fracture-reduction benefits seen in the clinical trials. After analysis of hundreds of studies, they found that highly compliant, “real world” patients on osteoporosis drugs experienced a 21% reduction in all clinical fractures. This compares to the 24% overall clinical fracture reduction experienced by subjects in osteoporosis drug clinical trials.

Now compare this 21-24% fracture-reduction benefit from bone drugs to the studies documenting that those taking vitamin D in any dose (much less a therapeutic dose) experience a 23-26% reduction in fractures.

These are quite different messages than the ones we often hear — how bone drugs reduce your chance of fracture by 50% or that they are much more effective than natural treatments.

You have choices about bone health

There is a lot of fear and anxiety around any osteoporosis or osteopenia diagnosis. It’s reassuring to know that your body is capable of building and strengthening bone on its own when given the needed support and time to do so. In the end, the choice is yours. The prescriptions advertised on television may sound and look enticing, but the benefits are often exaggerated.

For over 25 years at our bone health center we have helped thousands of women strengthen their bones and prevent fracture — and 90% of them have not needed drugs.

References

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2 Ott, S. 2007. Bisphosphonates: Effects on bones. Bisphosphonate structure. URL: http://courses.washington.edu/bonephys/opbis2.html (accessed 07.31.2008).

3 Russell, R. 2006.

  Rogers, M. 2003. New insights into the molecular mechanisms of action of bisphosphonates. Curr. Pharm. Des., 9 (32), 2643–2658. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/14529538 (accessed 08.05.2008).

  Fisher, J., et al. 1999. Alendronate mechanism of action: Geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc. Natl. Acad. Sci. USA, 96 (1), 133–138. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/9874784 (accessed 08.05.2008).

  Luckman, S., et al. 1998. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J. Bone Miner. Res., 13 (4), 581–589. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/9556058 (accessed 08.05.2008).

  van Beek, E., et al. 1998. Binding and antiresorptive properties of heterocycle-containing bisphosphonate analogs: Structure–activity relationships. Bone, 23 (5), 437–442. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/9823450 (accessed 08.05.2008).

  Rodan, G., & Fleisch, H. 1996. Bisphosphonates: Mechanisms of action. J. Clin. Invest., 97 (12), 2692–2696. URL (PDF): http://www.jci.org/articles/view/118722/pdf (accessed 08.05.2008).

4 Ott, S. 2007. Bisphosphonates: Effects on bones. Bisphosphonate structure. URL: http://courses.washington.edu/bonephys/opbis2.html (accessed 07.31.2008).

5 Bauer, D., et al. 2006. Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture intervention trial. J. Bone Miner. Res., 21 (2), 292–299. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/16418785 (accessed 08.05.2008)

  Bauer, D., et al. 2004. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: The Fracture Intervention Trial. J. Bone Miner. Res., 19 (8), 1250–1258. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/15231011 (accessed 08.05.2008).

6 Kwek, E., et al. 2008. An emerging pattern of subtrochanteric stress fractures: A long-term complication of alendronate therapy? Injury, 39 (2), 224–231. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/18222447 (accessed 08.04.2008).

  Neviaser, A., et al. 2008. Low-energy femoral shaft fractures associated with alendronate use. J. Orthop. Trauma, 22 (5), 346–350. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/18448990 (accessed 08.04.2008).

  Parker–Pope, Tara. 2008. Drugs to build bones may weaken them. New York Times, July 15, 2008. URL: http://www.nytimes.com/2008/07/15/health/15well.html?partner=rssnyt&emc=rss (accessed 07.29.2008).

  Cheung, R., et al. 2007. Sequential nontraumatic femoral shaft fractures in a patient on long-term alendronate. Hong Kong Med. J., 13 (6), 485–489. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/18057440 (accessed 08.04.2008).

7 McClung, M., et al. 2004. Prevention of postmenopausal bone loss: Six-year results from the Early Postmenopausal Intervention Cohort (EPIC) study. J. Clin. Endocrinol. Metab., 89 (10), 4879–4885. URL: http://jcem.endojournals.org/cgi/content/full/89/10/4879 (accessed 08.05.2008).

8 Wells, G., et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst. Rev., 23 (1). URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/18253985 (accessed 08.05.2080).

9 Wieand, H. 2003. Is relative risk reduction a useful measure for patients or families who must choose a method of treatment? J. Clin. Onc., 21 (23), 4263–4264. URL: http://jco.ascopubs.org/cgi/content/full/21/23/4263 (accessed 08.05.2008).

10 MacLean, C., et al. 2008. Systemic review: Comparitive effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann. Intern. Med., 148 (3), 197–213. URL (abstract): (accessed 08.11.2008).

  Cummings, S., et al. 1998. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. JAMA, 280 (24), 2077–2082. URL: http://jama.ama-assn.org/cgi/content/full/280/24/2077 (accessed 08.07.2008).

11 Alonso–Coello, P., et al. 2008. Analysis. Drugs for pre-osteoporosis: Prevention or disease mongering? BMJ, 336 (7636), 126–129. URL: http://www.bmj.com/cgi/content/full/336/7636/126 (accessed 08.06.2008).

12 Heckbert, S., et al. 2008. Use of alendronate and risk of incident atrial fibrillation in women. Arch. Intern. Med., 168 (8), 826–831. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/18443257 (accessed 08.05.2008).

  Ott, S. 2008. Bisphosphonates. URL: http://courses.washington.edu/bonephys/opbis.html#side (accessed 08.05.2008).

13 Melton, L., et al. 1998. Long-term trends in hip fracture prevalence: The influence of hip fracture incidence and survival. Osteoporos. Int., 8 (1), 68–74. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/9692080 (accessed 08.05.2008).

14 Sehgal, A. 2008. Prevalence of US osteoporotic hip fracture hospitalizations declines despite an ageing population. URL: http://www.medicalnewstoday.com/articles/111030.php (accessed 08.05.2008).

15 Nelson, N. 2007. Osteoporosis. Second thoughts: Some women resist advice to try drugs. Washingtonpost.com, June 12, 2007. URL: http://www.washingtonpost.com/wp-dyn/content/article/2007/06/11/AR2007061101927.html (accessed 08.01.2008).

16 Alonso–Coello, P., et al. 2008.

17 Liebman, M. 2002. Awakening the silent osteoporosis market. Medical Marketing & Media. URL: http://www.allbusiness.com/medicine-health/diseases-disorders-musculoskeletal/10599376-1.html (accessed 08.05.2008).

18 Dach, J. 2007–2008. Reversing osteoporosis naturally: Diagnostic testing bone density scan. URL: http://www.drdach.com/wst_page6.html (accessed 08.01.2008).

19 Carmona, R. 2004. Bone health and osteoporosis. A report of the Surgeon General. URL: http://www.surgeongeneral.gov/library/osteoporosisandbonehealth/content.html (accessed 08.05.2008).

20 Brown, S. 2008. Vitamin D and fracture reduction: An evaluation of the existing research. Alt. Med. Rev., 13 (1), 21–33. URL (PDF): http://www.thorne.com/altmedrev/.fulltext/13/1/21.pdf (accessed 01.20.2009).

Further reading

  • Fehm, T., et al. 2009. Bisphosphonate-induced osteonecrosis of the jaw (ONJ): Incidence and risk factors in patients with breast cancer and gynecological malignancies. Gynecol. Oncol. [Epub ahead of print.] URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/19136147 (accessed 01.13.2009).
  • Sedghizadeh, P., et al. 2009. Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw: An institutional inquiry. J. Am. Dent. Assoc. 140 (1), 61–66. URL (abstract): http://www.ncbi.nlm.nih.gov/pubmed/19119168 (accessed 01.05.2009).
  • Weinstein, R., et al. 2009. Giant osteoclast formation and long-term oral bisphosphonate therapy. NEJM, 360 (1), 53–32. URL: http://content.nejm.org/cgi/content/full/360/1/53 (accessed 01.02.2009).

  See also:
  Glowacki, J. 2009. The deceiving appearances of osteoclasts. NEJM, 360 (1), 80–82. Editorial. URL: http://content.nejm.org/cgi/content/full/360/1/80 (accessed 01.02.2009).

  • Wysowski, D. 2008. Reports of esophageal cancer with oral bisphosphonate use. NEJM, 360 (1), 89–90. Correspondence. URL: http://content.nejm.org/cgi/content/full/360/1/89 (accessed 01.02.2009).