The Diagnosis of Osteoporosis: Identifying the patient at high risk of fracture

Jonathan D. Adachi M.D., FRCPC
Professor, Department of Medicine
St. Joseph's Health Care - McMaster University
Hamilton, ON

Alexandra Papaioannou, M.D., FRCPC
Associate Professor, Department of Medicine
Hamilton Health Sciences - McMaster University
Hamilton, ON

Definitions
In a 1993 consensus conference, osteoporosis was defined as a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a resultant increase in fragility and risk of fracture1. More recently the National Institutes of Health consensus conference modified this definition to reflect that bone strength is more than just bone density and introduced the concept of bone quality2. They defined osteoporosis as follows: a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength reflects the integration of two main features: bone density and bone quality.

Probably, the only clinically applicable index of bone quality at present is a patients history of a fragility fracture. A fragility fracture may be defined as one that occurs as a result of minimal trauma, such as a fall from a standing height or less, or occurs without identifiable trauma.

Given the absence of applicable measures of bone quality in practice, the diagnosis of osteoporosis tends to be made on the basis of low bone density. WHO definitions are used in interpreting BMD which are based on a comparison of a patients BMD with the mean for a normal young adult population of the same sex and race3,4. The patient is assigned a T-score, which is the number of standard deviations above or below the mean BMD for normal young adults as follows:

  1. Normal BMD is defined as a T-score between +2.5 and 1.0 (i.e., the patients BMD is between 2.5 standard deviations (SDs) above the young adult mean and one SD below the young adult mean).
  2. Osteopenia (low BMD) is associated with a T-score between 1.0 and 2.5, inclusive. Osteopenia is also a term used by radiologists to indicate that the bones on a plain X-ray film appear to be of decreased mineral content.
  3. Osteoporosis is defined as a T-score lower than 2.5.

Severe osteoporosis describes patients whose T-score is below 2.5 and who also have suffered a fragility fracture.

The Diagnosis of Osteoporosis
Historically, osteoporosis was diagnosed late in the course of the disease when bone had become weakened to the point of fracturing. With the WHO definition of osteoporosis, diagnosis now depends on measurement of BMD. The classification is based on the risk of fracture considering BMD alone. Incidentally, this shift in the emphasis from osteoporosis to fragility has caused confusion. On occasion, a patient that had a fracture, was not diagnosed with osteoporosis and thus not offered treatment because of a BMD that was not within the osteoporotic range.

Osteoporosis Canada, previously known as the Osteoporosis Society of Canada, recognized that it was fractures that caused disability and reductions in quality of life. Fractures were the clinically relevant patient outcomes and while they continued to define osteoporosis based on T-scores, they also highlighted key risk factors for developing fractures5.

Four Key Risk Factors for Fracture
After reviewing the literature and considering the effect of potential confounders, Osteoporosis Canada identified four key factors as predictors of fracture related to osteoporosis: low BMD, prior fragility fracture, age and family history of osteoporosis. Other factors that are commonly cited risk factors were not found to be consistent independent predictors of fracture risk, after taking into consideration age and/or BMD.

BMD
The techniques for measuring bone density may be divided into those that measure the central skeleton (spine, proximal femur, whole skeleton, etc.) and those that measure some part of the peripheral skeleton. Measurement of the central skeleton is most widely carried out using dual-energy X-ray absorptiometry (DXA). DXA bone measurement (with consideration of age) is the most effective way to estimate fracture risk in postmenopausal Caucasian women6,7.

The relation between BMD and fracture risk has been calculated in a large number of studies. A meta-analysis of some of the earlier studies still represents the best estimate5. BMD is clearly the most readily quantifiable predictor of fracture risk for those who have not yet suffered a fragility fracture. For each standard deviation of BMD below a baseline level, the fracture risk approximately doubles. This risk should always be viewed in the context of the persons age. For example a 25 year old with a low BMD (e.g., a T-score of 2.5) has a very low 10-year risk of fracture that is not appreciably greater than that of a 25 year old with a high BMD. However, a person with the same BMD at age 65 has a much higher 10-year risk of fracture.

It is clear from epidemiology studies that age is a major risk factor for fracture. Because low BMD is also a major risk factor for fracture and BMD decreases with age, there must also be an age at which it is worthwhile to begin using BMD as a screening tool. Osteoporosis Canada has taken the position that BMD testing is appropriate for targeted case-finding among people under age 65 and for all women age 65 and older because of the high risk of osteoporosis and fracture after that age5.

Prior Fragility Fracture
Established osteoporosis may still be recognized on radiographs of the spine. However, because some two thirds of spinal fractures are not diagnosed clinically, one cannot rely on radiographs obtained to investigate back pain. Although there is some debate over what constitutes a vertebral fracture deformity, the most widely used criterion is derived from measurements of the vertical height of a vertebra at its anterior margin, centre (or midposition) and posterior margin on lateral spine radiographs. If these measurements differ from each other or from the same measurements in the supra- or sub-adjacent vertebrae by 20% or more, the vertebra is considered to have a fracture deformity if congenital, developmental, degenerative or other causes of such deformities are excluded8. Evidence shows that the presence of one such prevalent fracture implies a risk of further fracturing that is equal to the risk associated with a BMD of one standard deviation below the mean peak density. Better recognition and measurement of vertebral deformities presents a major opportunity for increased early recognition of osteoporosis.

A prior fragility fracture places a person at 1.5 to 9.5 fold increased risk for another one depending on the age at assessment, number of prior fractures and the site of the incident fracture8-14. For example the presence of a vertebral fracture increases the risk of a second vertebral fracture at least four-fold15,16 and 20% of those who experience one vertebral fracture will have a second vertebral fracture within one year17. Vertebral fractures are also indicators of increased risk of fragility fractures at other sites, such as the hip18. In one study, the combination of a vertebral fracture and low bone density was associated with a doubling of the three-year risk of hip fracture (from 3% to 6%) in women over the age of 7018. Similarly, wrist fractures predict vertebral and hip fractures11. Patients with a hip fracture are at increased risk of a second hip fracture. Pooling the results from all studies and for all fracture sites, the risk of subsequent fracture among those with a prior fracture at any site is 2.2 times that of people without a prior fragility fracture (95% confidence interval [CI] 1.92.6)11.

Age
Age is a major contributor to fracture risk. The ten-year probability of experiencing a fracture of forearm, humerus, spine or hip increases as much as eight-fold between ages 45 and 85 for women and five-fold for men19. As pointed out earlier, the risk of fracture based on BMD measurements should not be made in isolation from age. Indeed a recent Osteoporosis Canada and Canadian Association of Radiologists clinical practice guideline clearly relates BMD T-scores to age in determining absolute ten-year fracture risk20.

Family History of Osteoporotic Fracture
This factor has been best studied with respect to hip fracture21. One study identified a maternal history of hip fracture as a key risk factor for hip fracture in a population of elderly women. A history of hip fracture in a maternal grandmother also carries an increased risk of hip fracture22. Although most studies have focused on the index persons mother or other female family members, genetic influence on the risk of osteoporosis is multi-factorial, and one should not ignore a history of osteoporotic fracture in first- or second degree male relatives. It is now clear that fractures are common in men; therefore, although the recommendations focus on hip fractures in a patients mother or grandmother, other family members should be included during assessment. Genetic influence on osteoporosis and BMD is extremely important; it has been estimated that heredity accounts for 5080% of the variability in BMD23. A number of genes have been associated with osteoporosis; however, they have not yet resulted in a clinical application in the diagnosis and treatment of osteoporosis at the practitioner level.

Summary
While we define osteoporosis as a lumbar spine or hip T-score of less than -2.5 SD below the young normal range, we have gone beyond this simple score. For the orthopaedic surgeon, this means that age and prior fragility fracture are particularly important in identifying those at increased risk for fractures, those who might well benefit from intervention.

References

  1. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:646-50.
  2. Osteoporosis prevention, diagnosis and therapy. NIH consensus statements 2000;17(1):1-45. [http://consensus.nih.gov/cons/111/111_intro.htm]
  3. Kanis J.A., Melton L.J. III, Christiansen C., Johnston C.C., Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994;9:1137-41.
  4. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO Study Group. Geneva: WHO; 1994. Tech. rep. series.
  5. Brown J.P., Josse R.J. for the Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002;167:S1-S34
  6. Marshall D., Johnell O., Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254-9.
  7. Torgerson D.J., Campbell M.K., Thomas R.E., Reid D.M. Prediction of perimenopausal fractures by bone mineral density and other risk factors. J Bone Miner Res 1996;11:293-7.
  8. Black D.M., Palermo L., Nevitt M.C., Genant H.K., Christensen L., Cummings S.R. Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1999;14:90-101.
  9. Wasnich R.D., Davis J.W., Ross P.D. Spine fracture risk is predicted by nonspine fractures. Osteoporos Int 1994;4:1-5.
  10. Davis J.W., Grove J.S., Wasnich R.D., Ross P.D. Spatial relationships between prevalent and incident spine fractures. Bone 1999;24:261-4.
  11. Klotzbuecher C.M., Ross P.D., Landsman P., Abbott T.A.I., Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 2000;15:721-39.
  12. Ross P.D., Davis J.W., Epstein R.S., Wasnich R.D. Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 1991;114:919-23.
  13. Tromp A.M., Smit J.H., Deeg D.J.H., Bouter L.M., Lips P. Predictors for falls and fractures in the longitudinal aging study Amsterdam. J Bone Miner Res 1998;13:1932-9.
  14. Fox K.M., Cummings S.R., Williams E., Stone K., Study of Osteoporotic Fractures. Femoral neck and intertrochanteric fractures have different risk factors, a prospective study. Osteoporos Int 2000;11:1018-23.
  15. Ettinger B., Black D.M., Mitlak B.H., Knickerbocker R.K., Nickelsen T., Genant H.K., et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA 1999;282:637-45.
  16. Black D.M., Arden N.K., Palarmo L., Pearson J., Cummings S.R. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. J Bone Miner Res 1999;14:821-8.
  17. Lindsay R., Silverman S.L., Cooper C., Hanley D.A., Barton I., Broy S.B.. Risk of new vertebral fracture in the year following a fracture. JAMA 2001; 285(3):320-3.
  18. McClung M.R., Geusens P., Miller P.D., Zippel H., Bensen W., Roux C., et al. Effects of risedronate on the risk of hip fracture in elderly women. N Engl J Med 2001;344:333-40.
  19. Kanis J.A., Johnell O., Oden A., Dawson A., De Laet C., Jonsson B. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001;12:989-95.
  20. Siminoski K., Leslie W.D., Frame H., Hodsman A., Josse R.G., Khan A., Lentle B.C., Lvesque J., Lyons D.J., Tarulli G., Brown J.P. Recommendations for Bone Mineral Density Reporting in Canada. Can Assoc Radiol J 2005;56:178188.
  21. Cummings S.R., Nevitt M.C., Browner W.S., Stone K., Fox K.M., Ensrud K.E., et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995;332:767-73.
  22. Torgerson D.J., Campbell M.K., Thomas R.E., Reid D.M. Prediction of perimenopausal fractures by bone mineral density and other risk factors. J Bone Miner Res 1996;11:293-7
  23. Patel M.S., Rubin L.A., Cole D.E.C. Genetic determinants of osteoporosis. In Henderson J.E., Goltzman D. (editors). The osteoporosis primer. Cambridge: Cambridge University Press; 2000:131-46.

 

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