clinical management.' Similar but more detailed studies have been done by others.24 Dr Law and colleagues fail to cite two of these studies and to discuss the opposite conclusion reached by all three. There are two major problems in Dr Law and colleagues' review which may apply to some "epidemiological" studies: firstly, lack of perspective is masked by averaging the results of multiple studies, including those that are defective, and, secondly, biases are supported by excluding contradictory studies. Meta-analysis in osteoporosis was initiated by Cummings,5 who claimed, as do Dr Law and colleagues, that diminution of bone does not predispose to hip fracture. Both

groups supported their position by excluding positive reports and by including only reports of studies that used early densitometers, which were inaccurate on the femur because of problems in determining soft tissue baselines and a reliable region of interest across the femoral neck. Dr Law and colleagues rejected three major studies that showed profound loss (40-45%) of bone mineral density in cases of hip fracturebut accepted the results from these same studies showing that bone mineral density at sites other than the femur was not reduced. The rationale given was that immobilisation after fracture decreased the bone mineral density of the contralateral femur. The authors neglect to consider, however, that (a) the contralateral femur is probably denser than the one that fractures and (b) hvpertrophy after fracture probably occurs in the good hip. On the other hand, Dr Law and colleagues accepted the study of Eriksson and Widhe, which used a reliable densitometer but had a "control group" of 39 patients with osteoporosis.9 The Z score in that study was -1 5, not 0 5, if the controls were normal women without fracture. Vega et al summarise the bone mineral density in 225 cases of hip fracture'; it was 0-58 g/cm2 for the femoral neck and 0-42 g/cm2 for Ward's triangle. This gives a Z score of 1 4 for both sites, not 0 5, or about 70% sensitivity at 90% specificity. Readers must judge for themselves if this is adequate for diagnostic use. When there is egregious selectivity, as in this report, all the aspects of the report must be thoroughly examined and the logic and assump-

tions questioned. One logical mistake is that a low Z score diminishes the value of bone densitometry. The ability to predict future morbid events can be determined only from prospective trials; the risk can be high even if there is overlap of distributions between affected patients and controls. For example, there is a low Z score for cholesterol in coronary heart disease and blood pressure in stroke. Would Dr ILaw and colleagues have clinicians forgo measurement of these risk factors as well? RICHARD B MAZESS

Lunar Corporation, Madison, Wisconsin 53713, United States 1 Law MR, Wald NJ, Meade TW. Strategies for prevention of osteoporosis and hip fracture. BAJ 1991;303:453-9. (24 August.) 2 Melton LJ, Eddy DM, Johnston CC. Screerning for osteoporosis. Ann Intern Med 1990;112:516-28. 3 Tosteson AN, Rosenthal DI, Melton LJ, Weinstein MC. Costeffectiveness of screening perimenopausal white women for osteoporosis: bone densitometrv and hormone replacement therapy. Ann Intern Med 1990;113:594-603. 4 Ross PD, Wasnich RD, MacLean CJ, Hagino R, Vogel JM. A model for estimating the potential costs and savings of osteoporosis prevention strategies. Bone 1988;9:337-47. 5 Cummings SR. Are patients with hip fractures more osteoporotic? AmJ Med 1985;78:487-94. 6 Vega E, Mautalen C, Gomez H, Garrido A, Melo L, Sahores AO. Bone mineral density in patients with cervical and trochanteric fractures of the proximal femur. Osteoporosis Int 1991;1:81-6. 7 Mazess RB, Barden HS, Ettinger M, Schultz E. Bone density of the radius, spine and proximal femur in osteoporosis. 7 Bone Miner Res 1988;3:13-8. 8 Meltzer M, Lessig HJ, Siegel JA. Bone mineral density and fracture in postmenopausal women. Calcif Tissue Int 1989;45: 142-5. 9 Eriksson SA, Widhe TL. Bone mass in women with hip fracture. Acta Orthop Scand 1988;59:19-23.

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AUTHORS'REPLY,-Dr Compston and Drs Stevenson and Marsh disagree with our conclusion on the rapid loss of protection from hip fracture after hormone replacement therapy is stopped. ' We think that they are incorrect. The best evidence comes from the observational studies of hip fracture, showing an approximate halving of risk with current use but little or no protection after therapy has been stopped for five or more years.2` The two randomised trials support this conclusion. In the study of Lindsay et al bone density remained at its initial value in women taking oestrogen for eight years, but in a group of women who took oestrogen for the first four years it declined after a further four years to a value similar to that in a randomised control group who took no oestrogens at all' (figure). The use of the metacarpal as a model is justified by the fact that this bone was responsive to oestrogen supplementation6 and by the finding that the metacarpal is a site of osteoporotic fracture, with an estimated relative risk per standard deviation decrease in bone density of 1 7 compared with 1-4 for the hip.7 43-

8

Oestrogen for

42-

8 years

40ia E




then no oestrogen for 4 years No oestrogen

38370

2

4 Years

6

8

Change in metacarpal bone mineralcontentovereightyears in three groups of women after oophorectomy given oestrogen for all eightyears, for thefirstfouryears, and not at all

The conclusion of Christiansen et al, cited in support of a long term effect of hormone replacement therapy, is not justified by their data.8 There was only one year's observation after hormone replacement therapy was stopped, and this tended to show a catch up rate of decline. Also, an observational study has shown faster bone loss in women after withdrawal of hormone replacement therapy than in untreated women.9 This effect is not surprising as bone loss is faster in women immediately after the withdrawal of oestrogensboth postmenopausal women and those who have stopped hormone replacement therapy-than it is several years thereafter. Dr Compston's view that the loss of protection from hip fracture after withdrawal of hormone replacement therapy cannot be assessed without information on the duration of therapy does not take into account that the analysis allows for age, so that the duration of hormone replacement therapy and time since stopping effectively measure the same thing, assuming that the age at the start of therapy tends to be constant, which in general is the case. We believe that Drs Stevenson and Marsh underestimate the effect of exercise in preventing osteoporotic fracture. The evidence from many sources is remarkably consistent. Observational studies, clinical trials, and animal data all show that exercise increases bone density. Six studies show a large reduction in the risk of hip fracture with habitual or occupational exercise. Of all the known causes of hip fracture, only exercise has shown changes that in time and magnitude could explain the doubling in the risk of hip fracture observed over 25 years. Other factors may well play a part, as the correspondents suggest, but the evidence that they do so is less complete and insufficient for their inclusion in a quantitative assessment of the potential for prevention available now. Dr Mazess makes various incorrect statements. The three studies he cites are not similar to ours in that none of them extensively review published data, and they do not reach the opposite conclusion;

indeed, one gives an estimate for the difference in bone density between cases of hip fracture and controls of about half a standard deviation, the same as our own, and concludes that unselective screening cannot be recommended at present.'" We did not claim that diminution of bone does not predispose to hip fracture; we emphasised that it does but showed that despite this it is an ineffective screening test. Bone density screening fails because all the elderly people in the community being screened will have similar low values, so that even if individual values in old age could be predicted at the menopause the discrimination that these values provide is too small. The estimated difference in femoral neck bone density between cases and controls of half a standard deviation falls so short of the requirement for an effective screening test that the specific points raised by Dr Mazess are immaterial. In any event, we think it unreasonable to include data on bone density in patients immobilised after a hip fracture; it is implausible that the femoral neck should "hypertrophy" over this period when immobility causes bone loss. Previous reviews of osteoporosis and hip fracture have emphasised the importance of hormone replacement therapy and exercise but have been more guarded over the value of bone density screening as a method of prevention. Our analysis of the evidence reinforces the importance of hormone replacement therapy with the qualification that its effect after withdrawal is less lasting than might previously have been thought; it emphasises the importance of exercise (which may previously have been underestimated) and the avoidance of smoking; and it shows that the performance of screening is too poor for it to be proposed as an instrument of national policy in the prevention of hip fracture. The correspondents' comments do not justify revision of this assessment of the potential for prevention. M R LAW N J WALD T W MEADE

Wolfson Institute of Preventive Medicine, Medical College of St Bartholomew's Hospital, London EC I M 6BQ I Law MR, Wald NJ, Meade TW. Strategies for prevention of osteoporosis and hip fracture. BMJ 1991;303:453-9. (24 August.) 2 Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980;303: 1195-8. 3 Paganini-Hill A, Ross RK, Gerkins VR, Henderson BE, Arthur M, Mack TM. Menopausal estrogen therapy and hip fractures. Ann Intern Med 1981;95:28-31. 4 Paganini-Hill A, Chao A, Ross RK, Henderson BE. Exercise and other factors in the prevention of hip fracture: the leisure world study. Epidemiology 1991 ;ii: 16-2 5. 5 Kiel DP, Felson DT, Anderson JJ, Wilson PWF, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women. N EnglJ Med 1987;317:1169-74. 6 Lindsay R, Hart DM, MacLean A, Clark AC, Kraszewski A, Garwood J. Bone responses to termination of oestrogen treatment. Lancet 1978;i: 1325-7. 7 Seely DG, Browner WS, Nevitt MC, Genant HK, Scott JC, Cummings SR. Which fractures are osteoporotic? In: Christiansen C, Overgaard K, eds. Osteoporosts 1990. Copenhagen: Osteopress, 1990:463-4. 8 Christiansen C, Christensen MS, Transbol I. Bone mass in postmenopausal women after withdrawal of oestrogen/ gestagen replacement therapy. Lancet 1981;i:459-61. 9 Horsman A, Nordin BEC, Crilly RG. Effect on bone of withdrawal of oestrogen therapy. Lancet 1979;ii:33. 10 Melton LJ, Eddy DM, Johnston CC. Screening for osteoporosis. Ann Intern Med 1990;112:516-28.

Accidental ingestion of methadone SIR,-In the past year we have seen two young children die after accidentally ingesting methadone. In both cases the parents were receiving methadone prescribed for their opiate addiction. Several points cause us grave concern. Methadone is often prescribed-as in the above cases-in plain screw top bottles which are not child resistant. Methadone is prescribed in quantities of up to

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300 ml (300 mg) per bottle. This may be a week's supply for a drug dependent adult, but 20-30 ml can be lethal to a small child. Methadone syrup tastes pleasant enough for children to consume 150-200 ml without complaint. Parents often delay bringing to hospital children who have taken methadone. Drug dependent adults who can tolerate large doses of the drug may assume that a child will "sleep it off," and parents may be deterred from taking a child to hospital because they know that their competence to look after the child will be questioned. We are not trying to imply that methadone users should not have the care of their small children, but some steps must be taken to protect these children. We strongly suggest that it should be a legal requirement that all methadone be prescribed in child resistant plastic bottles. Further, methadone should be bitter to taste. Finally, very serious consideration should be given to limiting the quantity prescribed at any one time to methadone users who are responsible for small children. ELIZABETH MOLYNEUX RONNIE AHERN BERYL BALDWIN Accident and Emergency Departmerit, Royal Liverpool Children's Hospital and Community Services Trust, Liverpool L12 2AP

SIR,-I congratulate Mr M D Laverick and colleagues on their article on methods currently being used to prevent thromboembolism in orthopaedics.' There is, however, one more factor, which is not mentioned-that is, the type of anaesthesia. In 1978, as part of a study on spinal anaesthesia and general anaesthesia,2 I estimated the incidence of deep vein thrombosis after hip replacement by using the fibrinogen uptake test and phlebography.3 Altogether 120 patients were studied, of whom 56 received a spinal anaesthetic and 64 a general anaesthetic. Operative blood losses were measured. No patient had thromboprophylaxis. Spinal anaesthesia was associated with both a lower frequency of thrombosis (19/56 patients v 36/64 patients, p