Benefits of Screening for Osteoporosis
By Marcus M. Reidenberg, MD, FACP
Weill Cornell CERT
Summary by Kathleen Mazor, EdD
HMO Research Network CERT
Osteoporosis is a metabolic bone disorder that results in decreased bone strength with increased risk for future fractures. The U.S. Preventive Services Task Force recently recommended screening some women for their risk of fracture so that those at high risk for fracture could be evaluated for preventive treatment (1). The women to be screened are those who have not had a diagnosis of osteoporosis made in the past and have no symptoms of bone disease at the time of screening. They should all be women over 65 who have, on average, a 9% risk as determined by their FRAX score of getting a fracture over the next ten years or younger women with the same 9% risk. Some risk factors that increase the FRAX score and thus risk of a future fracture are having a parent with fractured hip, smoking, taking adrenal steroid hormones, having rheumatoid arthritis, and drinking 3 or more drinks of alcohol daily. The Task Force also concluded that there was too little information to know if screening helped men (1).
Anyone can find out one’s risk by using the FRAX calculator at: http://www.shef.ac.uk/FRAX/tool.jsp?country=9.
The way to screen is to measure the bone mineral density using special X-ray techniques called dual x-ray absorptiometry or DXA. The measurement of bone mineral density is named the “T score” A low score compared to a large group of healthy women predicts an increased risk of future fractures. What is the risk and how much does treatment help?
The FRAX calculator shows the chance one will get any fracture over the next ten years and also the chance that one will get a hip fracture over this same period of time.
There are many medicines that increase bone density and reduce the risk of fractures. One class of drugs has been extensively studied and is widely prescribed. It is the bisphosphonates. Some drugs in this class are: alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel, Atelvia), and zoledronic acid (Reclast).
A major study of alendronate or placebo given for three years to 4432 post-menopausal women was called the Fracture Intervention Trial. It has shed much light on the benefits of this class of medications. All women who entered the trial had low bone density at the start. Some had prior vertebral fractures and some did not. Since those with fractures at the start were at higher risk for another fracture than those without, they were analyzed separately.
For those with earlier fractures, there were 1022 women in the placebo group and they had 145 new fractures in the three years of the study. The 1005 women in the alendronate-treated group had 78 new fractures. There are three common ways to present these results. The risk of new fracture was 15% in the placebo-treated women and 8% in the alendronate-treated, a 7% actual or absolute difference. Another way is to say that it is 7% / 15% or 47% difference. This is the relative risk reduction produced by the drug. Expressing relative risk reduction makes a drug look much more effective than expressing absolute difference. This is why many studies present results as relative risk reduction even if it is not called by that name. The third way to present these results is by how many people must be treated to prevent one fracture. This is called the “number needed to treat” often seen as “NNT”. In this study, 15% of placebo-treated patients developed fractures. Only 8% of the alendronate-treated patients developed fractures. So 15% -8% equals 7%. Seven fractures were actually prevented out of 100 treated people. This means that one fracture was prevented per 14 people treated for 3 years. In other words, on average, one must treat 14 women with alendronate for 3 years to prevent one fracture in this group (2). The number needed to treat is 14 for 3 years. This number can vary with the severity of the osteoporosis in the group.
Women without earlier fractures are at lower risk of a new fracture than women who have already had a fracture. For these women, 2218 given placebo had 390 fractures (18%) and 2214 receiving alendronate had 315 fractures (14%). Thus the absolute risk reduction is 4%, the relative risk reduction is 28% and the NNT is 25 patients for 3 years to prevent one fracture. Further analysis of this group showed that only those women with very low bone density with a T score below -2.5 received this benefit. Those with less reduced bone density on drug had no decrease in their fracture rate than women taking placebo and were at the same risk for adverse effects as the patients with low bone density who did reduce their fracture risk. Women with T scores above -2.5 had risk for adverse effects but no demonstrated benefit from this drug. In addition, it is not clear at this time if bisphosphonate therapy should be continued beyond 5 years of treatment or if a drug holiday for a year or two helps to limit toxicity. Discontinuing alendronate after 5 or more years of therapy resulted in minimal bone loss over the next 3-5 years (4).The longest clinical trials lasted 5 years so evidence is lacking about the risks and benefits of continuous therapy for a longer period of time (5).
Side effects of the oral versions of this class of drugs are mainly gastrointestinal troubles from GI distress to acid reflux to ulcers in the esophagus, the tube leading from the throat to the stomach. These drugs must be swallowed with a full glass of water and then the patient must stay upright for 30-60 minutes. This is to keep the drug from irritating and even damaging the upper part of the digestive system, especially the esophagus. Other side effects are less common. One is a “flu-like” illness for a few days at the beginning of therapy. Rare bone events that occur more often in treated patients but are not proven to be caused by these agents include a disorder of the jaw bone often associated with dental procedures or poor oral hygiene and an atypical fracture of the thigh bone (6,7).If people without symptoms of bone disease are at high risk of fracture, taking a medicine in this class significantly lowers the risk. Taking the medicine with a full glass of water and then remaining upright for an hour substantially lowers the risk of GI side effects increasing the benefit to risk ratio. This is the way to take this medicine to gain the benefit while lowering the risk of side effects.
- U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011 Mar 1;154(5):356-64.
- Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996 Dec 7;348(9041):1535-41.
- Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998 Dec 23-30;280(24):2077-82.
- Rosen CJ. Postmenopausal osteoporosis. N Engl J Med 2005; 353:595-603.
- Qaseem A, Snow V, Shekelle P, Hopkins R Jr, Forciea MA, Owens DK. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008; 149: 404-15.
- Strampel W, Emkey R, Civitelli R. Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf. 2007;30(9):755-63.
- Schilcher J, MichaŽlsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011 May 5;364(18):1728-37.
This note can be found online at http://www.weill.cornell.edu/cert/patients/osteoporosis_screening.html
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