Summary of Session II and Concluding Remarks Steven Cummings, MD, San Francisco, California

ertebral fractures cause substantial morbidity; ~owever, it is difficult to define precisely how

much disability they cause. As Dr. Ross discussed, uncontrolled clinical series do not provide sufficient information. Observational studies cannot distin- guish morbidity caused by other illnesses that ac- company aging. The best approach for estinmting the impact of vertebral fractures may be to measure comprehensively the morbidity associated with ver- tebral fractures in randomized clinical trials of bone- specific agents.

The importance of "comorbidi ty" was emphasized in several discussions. A concer ted effort to treat comorbidi ty may be one of the most fruitful ways of improving outcome after hip fracture; it may even help to prevent hip fractures, particularly in men.

Dr. Lyons pointed out the regional variability in hip fracture management and how current treat- ments are based on anecdote, habit, and culture. Re- sults of treatlnent remain poor despite new ad- vances. Dr. Lyons also highlighted growing evidence that cemented may be bet ter than m~cemented pros- theses. Again, this theory would best be tested in randomized clinical trials.

Intensive home-based rehabilitation after a hip fracture appears to be a promising approach. It is attractive because it is likely to be less expensive than in-hospital care. Preliminary results suggest that home-based rehabilitation improves patient out- conies.

Dr. Tamayo discussed the management of patients with vertebral fractures. For asymptonmtic patients, the goal of treatment is to prevent new fractures. He proposed that some patients who are acutely symp- tomatic because of vertebral fracture need surgical stabilization of the spine. This concept needs careful study before it is applied to patients, because there is limited evidence supporting the benefits of surgi- cal stabilization. Benefits will depend on the risk of development of neurologic symptoms as a conse- quence of fracture. In general, this risk is probably very low.

From the Department of Medicine and Epidemiology, University of Cali- fornia, San Francisco, California.

Requests for reprints should be addressed to Steven Cummings, MD, Department of Medicine and Epidemiology, University of California, San Francisco, 74 New Montgomery Street, Suite 600/PSG, San Francisco, California 94105.

For all pat ients with chronic pain associated with vertebral fractures, Dr. Tanlayo's reconmlended multidisciplinary approach to management of symp- toms, improvement of muscular function, and treat- ment of os teoporosis may be useful. However, this would be an expensive undertaking because the problem occurs so frequently. Trials are needed in which rehabilitation is compared with maintenance of usual activity to help identify the best approach to management of symptomat ic vertebral fractures.

Given the likely deformity, loss of height, and chronic pain resulting f rom vertebral fractures, treat- ing patients with these fractures with the goal of pre- venting future fractures will have substantial benefit. This raises the issue of whether screening for ver- tebral fractures is worthwhile. It may be cost-effec- tive for pos tmenopausa l women to have radiographs when they develop new back pain. This question de- serves careful analysis because it could chm~ge the common pr imary care pract ice of managing back pain without radiographs.

There are many risk factors for hip fracture and, as Dr. Slemenda pointed out, many can be modified. Dr. Slemenda emphasized the potential value of physical activity for hip fracture prevention, building the case that we should encourage aging patients to exercise regularly.

It was proposed that modification of risk factors may add value to effective pharmacologic therapy; however, it is not clear whether risk factor modifi- cation would enhance very effective pharmacologic agents. If a risk factor worked by means other than altering bone mineral density, for example, by re- ducing the risk of falling, its modification might be more valuable.

The lasting credibility of the work that we do will depend on how much attention we pay to rigorous study design. Dr. Seeman pointed out how many tri- als have been flawed. We need to design and plan trials with care, and to pe r fonn post hoc analysis of data in a conservative fashion.

Dr. Seeman made the points that alendronate and estrogen are effective and that the effectiveness of alendronate is based on well-designed trials. Another key point is that t rea tments must be very safe, in particular when they are used for prevention, namely, in populat ions at relatively low risk, and for many years.

The next phase of trials in this field may be un- der taken to test whether anabolic agents added to

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SYMPOSIUM ON OSTEOPOROSIS/CUMMINGS

either alendronate or es trogen would substantially reduce fracture risk beyond the reduction attained with the use of alendronate or estrogen alone. As pointed out by Dr. Black, future trials of fracture pre- vention should also assess pain, function, and quality of life.

DISCUSSION Kyphosis for Screening Phi l ip D. Ross, PhD (Honolulu, Hawaii): In con- trast to the number of vertebral f ractures as a pre- dictor of outcome, the quantitative measure of ky- phosis, al though associated with advanced age and low bone density, has no associat ion with the fre- quency or severity of pain, nor with self-rated poor health. Therefore, kyphosis may be more a function of posture and general self-perception than an indi- cator of osteoporosis . Cyrus Cooper, FRCP (Southampton, United Kingdom): However, kyphosis is associated with a number of defornfities in 2 studies. Steven Cummings, MD (San Francisco, Califor- nia): We found that kyphosis is associated with tho- racic vertebral fractures. We were able to focus on kyphosis in the region where the fracture had oc- curred, and kyphosis was more often associated with a wedge-type fracture. This relationship does make sense; however, it is still not a very strong one. What Dr. Cooper says seems to be true, namely, that ver- tebral fractures explain only par t of kyphosis. Dr. Ross : For practical application, I p ropose it is bet ter to use a radiograph to look for fractures than to try to evaluate a pat ient based on the measure- ment of kyphosis.

Radiographs To Detect Vertebral Fractures Dr. C u m m i n g s : In pr imary care, the guidelines rec- onmlend taking radiographs for patients who have fever, tenderness, cancer, or other severe illness, and for the very elderly but not for pos tmenopausa l women per se. Dav id B. Ka rp f , MD ( R a h w a y , New Jersey): The routine use of radiographs for all pos tmenopausa l women with back pain could be an improvement , I think, because it will enable us to identify more high- risk people who might benefit f rom treatment. It would not be a perfect system, however, because only about 30% of fractures are symptomatic , yet the risk a t tendant to a prevalent fracture applies equally to asymptomat ic and symptomat ic fractures. Dr. C u m m i n g s : About 30% of patients with vertebral fractures get a medical diagnosis of fracture. I would suspect that the propor t ion who are symptomat ic is much higher than that. Dr. Karp f : In the Fracture Intervention Trial, 30% are acutely symptomatic . l

Dr. C u m m i n g s : In the Study of Osteoporot ic Frac- tures, it seems as though many, if not most , of the patients who are in the undiagnosed category have exper ienced increased back pain or a new onset of back pain during the study, but they did not get a medical diagnosis. The magnitude of that problem, I think, needs to be described.

Screening Ego Seeman, MD (Melbourne, Australia): Screening must result in a reduct ion in fracture in- cidence to be justified. There is no exper imental ev- idence to support this notion. Problems with the up- take and compliance with screening programs and drug treatment, and the modes t efficacy of treat- ments, suggest that screening may not be an effec- tive approach to fracture prevention. Based on theo- retical considerat ions published by Dr. Steve Cummings, 2 assuming a rate of 500 hip f ractures per year among 100,000 pos tmenopausa l women, if t rea tment is given to pat ients in the lower BMD ter- tile with a relative lifetime hip fracture risk of 2, and if hormone rep lacement therapy (HRT) halves the risk, a 40% compliance rate results in prevent ion of only 33 of the 500 hip fractures. Recently, Dr. Cooper published a theoretical analysis of the cost-effective- ness of a screening program among 100,000 women aged 45 years assuming that: 72% of the populat ion would be contacted and attend the program for screening and advice, 10 years of HRT would reduce fracture rates by 50%, and compliance with HRT would be 10-50%. 3 For any level of compliance, uni- versal HRT t rea tment gave a greater reduction of f ractures than screening, but even with 50% compli- ance, universal t rea tment would reduce fractures only by 18%. At compliance exceeding 10%, screen- ing and selective t rea tment were more cost-effective; at compliance of 10% or less, universal therapy would be more cost-effective. If screening of BMD were to enhance compliance, the proport ion of frac- tures averted would increase. Dr. C u m m i n g s : If getting a prescr ipt ion for the t rea tment is largely contingent on being screened, then screening will substantially increase prescrip- tion of the treatment. Compliance would be a prob- lem for those who are prescr ibed the t rea tment with or without screening. If access to screening is lim- ited, then you only reduce the application to a pop- ulation if you make all t rea tment contingent on get- ting screened. But, if other people who would benefit can be identified on the basis of factors other than screening densitometry, this could have a positive public health impact. That is the point of this. It is not an argument against screening; rather, it is point- ing out that screening can somet imes get in the way when the technology is limited.

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Dr. S e e m a n : Successful screening requires that each step is successful: a t tendance at screening and uptake and compliance with a drug that is safe, free of side effects, and effective. Dr . C u m m i n g s : There are a couple of studies, in- cluding a randomized trial to be p re sen t ed at the upcoming meet ing of the Amer ican Society of Bone and Mineral Research, 4 that demons t r a t e that there is a modes t increase in the up take of the rapy among pat ien ts w h o have low bone densi ty on screening. Dr. S e e m a n : There also are data that people who do not at tend screening programs have lower bone mass than those who do a t t end) Dr. Cummings : Yes. This implies that the most ef- fective progranls would reach out and try to at tract

women who would generally not seek out a screen- ing center.

REFERENCES 1. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lan- cet. 1996;348:1535-1541. 2. Cummings SR. Prevention of osteoporotic fractures: what we need to know. In: Christiansen C, Overgaard K, eds. Osteoporosis 1990. Third Symposium on Osteoporosis. Copenhagen, 1990:48-54. 3. Garton M J, Cooper C, Reid D. Perimenopausal bone density screening--will it help prevent osteoporosis? Maturitas. 1997;26:35-43. 4. Reid DM, Torgerson D J, Thomas RE, Campbell MK. Randomised trial of perimenopausal screening for osteoporosis risk: effect on HRT uptake and qual- ity of life. (Abstr.) Proceedings of the American Society of Bone and Mineral Research, 1996. 5. DiJppe H, G~rdsell P, Hanson BS, et al. Importance of participation rate in sampling of data in population based studies, with special reference to bone mass in Sweden. J Epidemiol Community Health. 1996;50:170-173.

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