Menopause Live (14 January, 2013) From IMS

In a study published last year, Margaret Gourlay and colleagues attempted to propose strategies for screening intervals of bone mineral density (BMD) testing [1]. Since then, the paper has been discussed in the correspondence section of the journal [2–5]. The authors analyzed data of 4957 women, 67 years of age or older, recruited in 1986 in the USA, who did not have osteoporosis at baseline, and who were followed longitudinally for up to 15 years within the Study of Osteoporotic Fractures (SOF) [6]. For this analysis, 49% of the total study population were excluded because they either already had osteoporosis, as defined by the World Health Organization (25%) [7] or treatment for osteoporosis or incomplete BMD data. BMD was measured by DXA at the femoral neck and total hip.

The primary outcome was to determine the BMD testing interval in these women, defined as the estimated time for 10% of the subjects to make the transition to osteoporosis from normal bone density or osteopenia at baseline, before a hip or clinical vertebral fracture occurred and before treatment for osteoporosis was initiated. The participants were stratified into four groups according to the T-score range (lowest T-score at femoral neck or total hip): normal BMD (T-score ≥ 1.00), mild osteopenia (T-score −1.01 to −1.49), moderate osteopenia (T-score −1.50 to −1.99), and advanced osteopenia (T-score −2.00 to −2.49). Sixty-two percent of women with advanced, 21% with moderate, and less than 5% with mild osteopenia, and not even 1% with normal BMD made the transition to osteoporosis. 

Referring to calculations with parametric cumulative incidence models, the authors conclude that osteoporosis would develop in less than 10% of older women during rescreening intervals of approximately 1 year for women with advanced osteopenia, 5 years for women with moderate osteopenia, and 15 years for women with normal bone density or mild osteopenia, and, thus, they propose such interval testing for each group.

Comment

A rapid response from the International Society for Clinical Densitometry (ISCD) summarized the concerns of many clinicians on these suggestions [8]: 

• Singular focus on BMD without inclusion of clinical risk factors would lead to underdiagnoses in many patients who need treatment. 
• Neither women with osteoporotic lumbar spine BMD nor women with morphometric vertebral compression fractures (up to 30% show densitometric osteopenia) would be identified. 
• Women ≥ 67 years of age with normal BMD or mild osteopenia, i.e. women who very likely would not lose much bone mass within their first 15 postmenopausal years, would very unlikely become osteoporotic within the next 15 years, unless they incur illnesses or require medications that adversely affect bone. The latter group would not be identified as patients at risk when relying on BMD only. The authors assert, though, that their estimates for BMD testing intervals proved to be robust after adjustment for major clinical risk factors, but they concede to clinicians choosing to re-evaluate patients before the estimated screening intervals if there is evidence of decreased activity or mobility, weight loss, or other risk factors not considered in their analyses.
• Younger postmenopausal women, who usually lose bone more rapidly, were not studied.

It has been widely accepted that fracture risk assessment should not be based solely on measuring BMD but on algorithms combining clinical risk factors with laboratory and DXA test results [2, 3]. Several prediction tools have been developed to assist physicians in evaluating a patient’s individual risk; none of them perfect, of course, considering the complexity of causal factors leading to osteoporotic fractures, but by far are more accurate than testing BMD alone [9]. Some risk factors do not translate into low BMD before fractures occur, e.g. type 2 diabetes, as reported recently [10]. High glucose levels in type 2 diabetes lead to accumulation of advanced glycosylation end-products (AGEs) in the organic bone matrix. Such AGE-distorted collagen affects bone to make it appear dense in DXA but render it more brittle and fragile. Thus, many patients with type 2 diabetes at risk for fractures would not be identified when focusing solely on BMD. 

The paper in discussion prompts the reader to question the category of ‘osteopenia’ as women with ‘mild osteopenia’ could well be allocated to the category ‘normal’ and, even more important, women with ‘advanced osteopenia’ to the category ‘osteoporosis’. Since the majority of fractures do not happen in patients with osteoporotic but with osteopenic or normal BMD values [11], many of them being also younger than 65 years of age, the focus should be on the detection of BMD changes per time unit in the early postmenopausal years, integrated to validated fracture risk models.

If the intention is to improve screening for fracture risk, a first BMD test should preferably be performed at around 55 years of age, combined with a compulsory and comprehensive evaluation of clinical risk factors. The interval to the next test should depend on the calculated individual risk and would mostly be scheduled between 1 and 5 years later. Therefore, the message delivered by the publication of Gourlay and colleagues gives the wrong signal to reimbursing authorities, which are fixated in most countries on thresholds of 65 years of age and BMD T-scores of -2.5.

Ewald Boschitsch
Head of the KLIMAX Menopause and Osteoporosis Clinic, Vienna, Austria

References

1. Gourlay ML, Fine JP, Preisser JS, et al. Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med 2012;366:225-33.
http://www.ncbi.nlm.nih.gov/pubmed/22256806
2. Cheung AM, Papaioannou A; Osteoporosis Canada Scientific Advisory Council Guidelines Committee. Bone-density testing interval and transition to osteoporosis. N Engl J Med 2012;366:1546; author reply 1547-8.
http://www.ncbi.nlm.nih.gov/pubmed/22512490
3. Lewiecki EM, Miller PD, Bilezikian JP. Bone-density testing interval and transition to osteoporosis. N Engl J Med 2012;366:1546-7; author reply 1547-8.
http://www.ncbi.nlm.nih.gov/pubmed/22512491
4. Yu EW, Finkelstein JS. Bone density screening intervals for osteoporosis: one size does not fit all. JAMA 2012;307:2591-2. Erratum in JAMA 2012;308:1432.
http://www.ncbi.nlm.nih.gov/pubmed/22735425
5. Gourlay ML, Preisser JS, Ensrud KE. Bone density testing in older women. JAMA 2012;308:1428-9.
http://www.ncbi.nlm.nih.gov/pubmed/23047349
6. Cummings SR, Black DM, Nevitt MC, et al. Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group. JAMA 1990;263:665-8.
http://www.ncbi.nlm.nih.gov/pubmed/2404146
7. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. 1994 World Health Organ Tech Rep Ser 843:1–129.
http://www.ncbi.nlm.nih.gov/pubmed/7941614
8. ISCD response to Gourlay et al. (NEJM 2012;366:225), 2012 Jan 20.
http://www.iscd.org/
9. Collins GS, Michaëlsson K. Fracture risk assessment: state of the art, methodologically unsound, or poorly reported? Curr Osteoporos Rep 2012;10:199-207.
http://www.ncbi.nlm.nih.gov/pubmed/22688862
10. Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res 2012;27:2231-7.
http://www.ncbi.nlm.nih.gov/pubmed/23023946
11. Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 2004;164:1108–12.
http://www.ncbi.nlm.nih.gov/pubmed/15159268