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BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXV NO. 3
11. Anonymous. Examinations. Lancet 1956;ii:
385-7.
12. Ziman J. Exams. Listener 1968;80:419-501.
13. Stone E. The evaluation of learning. BrJMed
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14. King LS. Medical thinking: a historical preface.
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Potter S, Bellamy N, and Buchanan WW. The
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Rheumatol 1977;4:l-3.
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Aequanimatas and other addresses. P.
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edn. 1914.
RHEUMATOID ARTHRITIS AND OSTEOPOROSIS
IN this edition there are two papers reporting
accelerated bone loss and increased skeletal
metabolism, together with two letters reporting
fractures, occurring in rheumatoid arthritis
(RA). In serial studies Reid etal. [1] have found
increased rates of bone loss at around 3-4% per
year, while Gevers et al. [2] have found elevated
serum osteocalcin levels, a noncollagenous
matrix protein which is produced by osteoblasts,
reflecting increased bone formation and hence
skeletal metabolism. While these studies appear
to be in good agreement, previous reports have
indicated that in RA skeletal metabolism may be
normal [3], increased [4] or suppressed [5]; that
serum calcium may be elevated [6] or low [7] and
that osteocalcin may be normal [3] or low [8]. A
histomorphometric study of rib biopsies showed
that bone formation was reduced, but resorption
rates were increased [9]. These results provide
conflicting data. There is no adequate explanation for this although the time after onset of
disease that is chosen for study may be relevant.
For example, following immobilization rapid
bone loss occurs but the skeleton eventually
becomes quiescent [10].
Thus, while there is little doubt that patients
with RA lose bone at an accelerated rate fl, 11],
have lower bone mass [12-rl4] and are at
increased risk of fracture [14-16], why the bone
loss should occur at all is not well established.
Periarticular osteoporosis, which may be due to
a local increase in vascularity, paracrine factors,
direct erosion by pannus and immobility of
affected joints, is a characteristic feature of RA
but the concept of a generalized alteration in
skeletal metabolism specifically related to the
disease is controversial. The problem is that
there are so many potential factors which may
contribute to bone loss—the patient's age, sex,
menopausal status [17], duration of arthritis
[18], coexistent disease, immobility, calcium
malabsorption [19], drugs, nutrition, vitamin D
status [14], etc. Osteoporosis is essentially a
disease of elderly women, and women with RA
who are postmenopausal will be at greatest risk.
Steroid therapy can cause accelerated bone loss,
although patients may have a variable skeletal
response to this drug [18]. Of the other factors,
immobility is likely to be the most important.
Rheumatoid arthritis is a multisystem disease
and it is clearly possible that there is skeletal
involvement. However, this issue cannot be
resolved on the basis of the data that are
currently available. With the newer techniques
of dual photon absorptiometry and computerized tomography, it is possible to measure
bone mineral at sites of clinical relevance such as
the spine and femur [20]. It is now recognized
that different rates of bone loss may occur at
various sites throughout the skeleton, e.g. in
postmenopausal osteoporosis there is predominantly spinal bone loss [21] while in anorexia
nervosa there is greater bone loss in the femoral
neck than in the spine, which has greater loss
than the distal radius [22]. Sodium fluoride and
low-dose parathyroid hormone, which have
241
EDITORIAL
been evaluated in the treatment of osteoporosis,
increase trabecular bone volume but apparently
at the expense of cortical bone [23]. To
obtain further information in RA, up-to-date
methodology should be used to study patients
with early disease at a time when they are fully
mobile. Nevertheless, in a study of early disease
(mean duration 14 months), reduced total body
potassium—an index of skeletal muscle mass—
was found [3] and it may not be possible to
eliminate the influence of mobility completely.
Ideally, patients should be premenopausal to
avoid the accelerated bone loss which occurs
following withdrawal of the protective effect of
oestrogen on the skeleton.
Why accelerated bone loss should occur is of
academic interest. It does occur and patients
sustain fractures, which is of practical relevance.
In a population who may already be elderly and
infirm, housebound and taking an inadequate
diet, a fracture may be a catastrophic event.
Currently, it is not possible to increase bone
mass predictably in patients with established
osteoporosis and it would therefore appear
likely that advances in therapy will need to be
related to prophylaxis. This may partially come
about by educating the population at large. Such
an approach seems possible since alteration in
diet appears to have been effective in reducing
coronary artery disease in the United States [24].
In preventing osteoporosis it is clearly desirable
that peak adult bone mass should be attained,
and it is probable that regular exercise and an
adequate calcium intake are important to the
growing skeleton [25]. Adults should also ensure
an adequate calcium intake, although the benefit
here is much more controversial [26]. In patients
with RA the importance of mobility should be
emphasized and an adequate diet ensured. However, in considering the prevention of bone loss,
most therapies will only have a trivial effect
when compared with oestrogen [27, 28]. The
possibility of routine oestrogen therapy in
women with RA at the time of the menopause
should be considered. Low-dose oestrogen
therapy is safe and, even if there is a small incidence of side-effects, this is surely an acceptable
price to pay when one considers that fracture of
the femur is now the leading cause of accidental
death amongst the elderly [29].
IGNAC FOGELMAN
Department of Nuclear Medicine,
Guy's Hospital,
London SE1 9RT, UK
REFERENCES
1. Reid DM, Kennedy NSJ, Smith MA, et al.
Bone loss in rheumatoid arthritis and
primary generalized osteoarthrosis: effects
of corticosteroids, suppressive antirheumatic drugs and calcium supplements. Br J
Rheumatol 1986;25:253-9.
2. Gevers G, Devos P, De Roo M, Dequeker J.
Increased levels of osteocalcin (serum bone
GLA-protein) in rheumatoid arthritis. Br J
Rheumatol 1986;25:260-2.
3. Sambrook PN, Ansell BM, Foster S, et al.
Bone turnover in early rheumatoid arthritis:
1. Biochemical and kinetic indexes. Ann
Rheum Dis 1985;44:575-9.
4. Steven MM, Sturrock RD, Fogelman I, Smith
ML. Whole-body retention of diphosphonate in rheumatoid arthritis. J Rheumatol
1982;9:873-7.
5. Heaney RP, Walch JJ, Steffes P, Skillman TG.
Periarticular bone remodelling in rheumatoid arthritis. Calcif Tiss Res 1968;
2(suppl):33-33B.
6. Kennedy AC, Allam BF, Rooney PJ, et al.
Hypercalcaemia in rheumatoid arthritis:
investigation of its causes and implications.
Ann Rheum Dis 1979;38:401-12.
7. Bramble MG, Blake DR, White T, Sly J, Kerr
DNS. Ionised calcium in rheumatoid arthritis: effect of non-steroidal anti-inflammatory
drugs. Br Med J 1980;281:840-l.
8. Riis BJ, Als OS, Christiansen C, Catherwood
BD, Deftos LJ. Bone turnover in rheumatoid arthritis. Calcif Tiss Int 1984;suppl2:
S4.
9. Duncan H, Frost HM, Villanueva AR, Sigler
JW. The osteoporosis of rheumatoid arthritis. Arthritis Rheum 1965;8(5):943-54.
10. Minaire P, Meunier P, Edouard C, Bernard J,
Courpron P, Bourret J. Quantitative histological data on disuse osteoporosis: comparison with biological data. Calcif Tiss Res
1974;17:57-73.
11. Vitiama P, Helela T, Kalliomaki JL.
Osteoporosis in rheumatoid arthritis. Acta
Rheum Scand 1968;14:276-84.
12. Bjelle AO, Nilsson BE. Osteoporosis in rheumatoid arthritis. Calcif Tiss Res 1970;5:32732.
13. Kennedy AC, Smith DA, Buchanan WW,
Anderson JB, Jasani MK. Bone loss in
patients with rheumatoid arthritis. Scand J
Rheumatol 1975;4:73-9.
14. Wordsworth BP, Vipond S, Woods CG,
Mowat AG. Metabolic bone disease among
in-patients with rheumatoid arthritis. Br J
Rheumatol 1984,23:251-7.
15. Taylor RT, Huskisson EC, Whitehouse GH,
Dudley Hart F. Spontaneous fractures of
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BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXV NO. 3
pelvis in rheumatoid arthritis. Br Med J
1971;4:663-4.
Maddison PJ, Bacon PA. Vitamin D deficiency,
spontaneous
fractures,
and
osteopenia in rheumatoid arthritis. Br MedJ
1974;4:433-5.
Stevenson JC, Whitehead MI. Postmenopausal osteoporosis. Br Med J 1982;
285:585-8.
McConkey B, Fraser GM, Bligh AS.
Osteoporosis and purpura in rheumatoid
disease: prevalence and relation to treatment with corticosteroids. Quart J Med
1962;124:419-27.
Sambrook PN, Abeyasekera G, Ansell BM, et
al. Calcium absorption in rheumatoid arthritis. Ann Rheum Dis 1985;44:585-8.
Fogelman I. Osteoporosis, bone mineral
measurements and photon absorptiometry.
Nucl Med Commun 1985;6:373-5.
Riggs BL, Wahner HW, Seeman E, et al.
Changes in bone mineral density of the proximal femur and spine with aging. J Clin
Invest 1982;70:716-23.
Treasure J, Fogelman I, Russell GFM.
Osteopenia of the lumbar spine and femoral
neck in anorexia nervosa. Scott Med J (in
press).
23. Karris JA. Treatment of osteoporotic fracture.
Lancet 1984;i:27-33.
24. Stamler J. Coronary heart disease: doing the
'right things'. N Engl J Med 1985;312:
1053-5.
25. Parfitt AM. Dietary risk factors for age-related
bone loss and fractures. Lancet 1983;ii:
26. Horsman A, Gallagher JC, Simpson M, Nordin BEC. Prospective trial of oestrogen and
calcium in post-menopausal women. Br Med
J 1977;2:789-92.
27. Lindsay R, Aitken JM, Anderson JB, Hart
DM, MacDonald EB, Clarke AC. Longterm prevention of postmenopausal osteoporosis by oestrogen: evidence for an
increased bone mass after delayed onset of
oestrogen treatment. Lancet 1976;i:103841.
28. Gordan GS. Osteoporotic bone loss. J Med
1980;ll:203-22.
29. Fardon DF, In: Osteoporosis. New York: Macmillan Publishing Company, 1985;3.
EDITORIAL NOTICE
IN order to accommodate an increasing demand for publication in the British Journal of Rheumatology, the Editorial Board has decided to increase the space available to contributors. As you can see
in the current edition this has been initially achieved by introducing two columns and a slightly
reduced type size. In 1987 and thereafter, the journal will be published on six occasions each year.
This policy will substantially reduce the waiting period between acceptance and publication of
original work.
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