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Home , Bone disease, Metabolic bone disease, Osteomalacia, Osteoporosis

Postgrad. med.J. (August 1968) 44, 621-625. Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from

Osteomalacia and D. B. MORGAN Department of Clinical Investigation, University ofLeeds

OSTEOMALACIA and osteoporosis are still some- in osteomalacia is an increase in the alkaline times confused because both diseases to a phosphatase activity in the blood (SAP); there deficiency of which can be detected on may also be a low serum or a low radiographs of the skeleton. serum calcium. This lack of calcium is the only feature Our experience with the biopsy of is that common to the two diseases which are in all a large excess of uncalcified bone tissue (), other ways easily distinguishable. which is the classic histological feature of osteo- malacia, is only found in patients with the other Osteomalacia typical features of the disease, in particular the Osteomalacia will be discussed first, because it clinical ones (Morgan et al., 1967a). Whether or is a clearly defined disease which can be cured. not more subtle histological techniques will detect Osteomalacia is the result of an imbalance be- earlier stages of the disease remains to be seen. tween the supply of and the demand for Bone , muscle weakness, Looser's zones, D. The the following description of disease is raised SAP and low serum are the Protected by copyright. based on our experience of twenty-two patients most reliable aids to the diagnosis of osteomalacia, with osteomalacia after ; there is no and approximately in that order. evidence that the features vary with the cause The interpretation of a raised SAP is difficult of the disease. because the 'normal values' for SAP are not The clinical features are nearly specific; the clearly defined. The particular problem is that common ones are bone pains and muscle weak- the SAP increases with age in the normal popula- ness. The bone pains are generalized, often worse tion (Hobson & Jordan 1959; Klaasen & Sier- at night, and sometimes associated with tender- stema, 1964); values of 16 or even 25 KA units/ ness of the . The bone pains have been 100 ml of serum are not uncommon in well mistakenly attributed to rheumatoid , persons over 60 years of age. Even if the SAP osteoarthritis or even neurosis, and the diagnosis of is above these values it may indicate some other osteomalacia may be delayed for years. disease of bone, for example Paget's disease, or The muscle weakness is most obvious in the even chronic , rather than osteo-

muscle around the , and a common symp- malacia. http://pmj.bmj.com/ tom is difficulty in climbing stairs and in sitting A raised SAP together with generalized bone up in bed without the aid of the arms. pains, could be the result of Paget's disease of The muscles may be wasted as well as weak bone rather than osteomalacia and it may be but there is usually no evidence of neurological impossible to distinguish these two diseases even damage; the weakness is a symptom of a primary on biopsy of the bone (Paterson, Woods & muscle disorder. The radiological signs of the Morgan, 1968). That Paget's disease is radiolog- disease may be no more than a generalized ically detectable is no proof that it is the cause lack of calcium in the skeleton indistinguish- of the symptoms and the presence of Paget's on September 28, 2021 by guest. able from that in osteoporosis. In addition, disease which is common does not exclude osteo- Looser's nodes are a radiological finding which malacia which is rare. is almost specific for osteomalacia. However, For these reasons we have come to regard a the nodes are not always present, and similar response to as the essential and final lesions arise in Paget's disease of bone, hyper- diagnostic criterion of osteomalacia. parathyroidism and thyrotoxicosis (Camp & Historically, osteomalacia was recognized as McCullogh, 1941). the adult counterpart of in children, that Looser's nodes are also known as pseudofrac- is to say osteomalacia was the result of a simple tures because they look like fractures on the deficiency of vitamin D usually the result of a radiographs, but they are often painless. poor dietary intake of the vitamin. Osteomalacia The common and constant biochemical change thus defined still occurs (Gough, Lloyd & Wills, 622 D. B. Morgan Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from

1964; Andersson et al., 1966; Chalmers et al., For the osteomalacia after gastrectomy we 1967). This condition can usually be cured with have given one dose of 10 mg of vitamin D2 by 3000 i.u. of vitamin D a day. The daily require- intramuscular injection. This dose will relieve ment for the vitamin in the diet is probably of the bone pains, heal the Looser's nodes, and the order of 100 i.u. (25,ug) in adults. Unfor- the SAP and serum phosphorus and calcium tunately, the term osteomalacia has been applied return to normal. The SAP may rise after the to those conditions which simulate nutritional vitamin D, before it begins to fall towards nor- osteomalacia in their clinical, biochemical, and mal values. The increase in the serum phos- histological signs, but which are not the result phorus may be the most dramatic and reliable of a simple deficiency of vitamin D. measure of a response to vitamin D but only if These 'osteomalacia-like' diseases fall into the measurements are made in the fasting patient. several groups according to the dose of vitamin The frequency at which further injections are D required to achieve some response and the required varies much from one patient to fundamental abnormality in the disease. another. We have controlled the frequency of At one extreme is the group of diseases which injection by the symptoms and the SAP. Some includes familial hypophosphataemia. These of our patients required the injections every 4 diseases are not cured by vitamin D however months, but one of our patients with severe much of the vitamin is given. osteomalacia, who had only one injection almost The osteomalacia of chronic glomerular failure 3 years ago, became symptom-free in a few heals with vitamin D but only in very large months and has remained well since. A safe doses (150,000i.u. a day or more). Stanbury & prescription and a liberal one would be an injec- Lumb (1966), therefore, suggested that this condi- tion of 1 mg of vitamin D2 every month. tion is the result of a resistance to the action Once the diagnosis is established it is essential of the vitamin and thus an increased demand to supplement the diet with calcium, otherwise Protected by copyright. for it. This demand is not met by the amount the bone may heal at the expense of the calci- of the vitamin in the diet. fied skeleton, and the osteomalacia may become The position within this spectrum of the osteoma- osteoporosis. lacia of intestinal disease depends on the form Treatment should be continued for at least 2 of the latter. Osteomalacia after resection of years, even if the symptoms have disappeared the distal intestine or in association with regional earlier and the biochemistry has returned to ileitis is usually the result of a simple deficiency normal. of vitamin D, perhaps due to a failure to absorb A recurrence of the disease can probably be the vitamin. On the other hand, the osteomalacia prevented by 1000 i.u. of vitamin D by mouth associated with due to sen- every day for life. Supplementation of the diet sitivity may be partly the result of a resistance with calcium is not necessary after the bones to the vitamin (Nassim et al., 1959). have healed. In order to establish the nature of the osteo-

malacia after gastrectomy we gave patients with The cause of the http://pmj.bmj.com/ the clinical and biochemical features of the We get our vitamin D from the diet by mak- disease, small doses of the vitamin of the order ing the vitamin in the skin through a trapping of the physiological requirement for the vitamin; of the energy in the ultraviolet light from the in this case 1000 i.u. (25 ,ug) weekly by intra- sun. muscular injection (Morgan et al., 1965b). The Taking into account the many factors which patients responded clinically, biochemically, diminish the amount of ultraviolet light that radiologically and histologically to this treat- reaches us, the amount of the vitamin we make ment. Such a response not only established the in the skin is probably small and may be insigni- on September 28, 2021 by guest. presence of osteomalacia in these patients but ficant in relation to our need for the vitamin. also demonstrated that the osteomalacia was Tthe deficiency of vitamin D in patients with the result of a simple deficiency of vitamin D. osteomalacia after gastrectomy is, therefore, the These small doses were chosen to establish result of too small an intake of the vitamin or the presence of a deficiency of the vitamin; we a failure to absorb the vitamin or both. would not of course suggest that they represent There is no simple explanation of the defic- the most efficient treatment for the disease. iency which applies to all patients with osteo- malacia after gastrectomy, and it seems likely The treatment of osteomalacia that a deficiency only arises when all the factors The dose of vitamin D which is effective which can diminish the supply of the vitamin clearly depends on the cause of the osteomalacia. coincide in one patient. Osteomalacia and osteoporosis 623 Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from The frequency of osteomalacia deformitities and fractures have been attributed In a survey of 1228 patients who had had a to the loss of bone together with a deterioration operation for peptic ulcer in York since in the quality of the bone tissue. But in the 1940 we saw only six patients with osteomalacia case of osteoporosis in the elderly there is no as we have defined it (Morgan et al., 1965a). great change in the quality of the bone and the None of these patients had had a vagotomy and failure of the bones is probably explained by the drainage procedure. We have since seen four loss of bone tissue. more patients with the disease so that the fre- In clinical practice, the diagnosis of osteopor- quency of osteomalacia after Polya-type gastrec- osis is applied in two distinct circumstances. The tomy was only about 1 % in men and 4 % in first is when the bones are found to be 'thin' on women. radiographs of the spine, taken for some unre- The disease was usually first obvious to the lated symptoms. The diagnosis in the second patient 8-12 years after operation. This is also group is based on the presence of complaints true of the other patients described in the litera- which are attributed to a loss of bone subse- ture and suggests that the patients who will later quently detected on radiographs. Thus backache develop osteomalacia are destined to do so from and rarely spine shortening and deformity are about the time of operation. attributed to vertebral collapse due to loss of There have been various opinions concerning bone from the vertebrae. Fractures of the long the existence and frequency of 'sub-clinical bones are attributed to a loss of bone tissue from osteomalacia' after stomach operations. the long bones. We have never denied the existence of a stage The question in dispute is whether there is a of osteomalacia where the biochemical and histo- distinct disease (osteoporosis) with a loss of logical changes are minimal but yet respond to much of the bone tissue, which can be detected the vitamin D. We have only one patient who might by histologist and the radiologist as a dis- Protected by copyright. have been at this stage of the disease. We, there- crete condition and which gives rise to symptoms fore, conclude that 'subclinical osteomalacia' which take the patient to the physician or the soon progresses to typical osteomalacia and orthopedic surgeon. would only be detected by chance. Thompson The reason for the dispute is that it is now and his colleagues (1966) suggested that sub- realized that there is a loss of bone tissue in all clinical osteomalacia is a common disease after persons as they age and it is not yet agreed gastrectomy. If this is so then in our experience whether this 'physiological' loss of bone is suffic- sub-clinical osteomalacia only rarely progresses ient to account for the clinical problem of to obvious osteomalacia. osteoporosis. Loss of bone tissue with age affects the Osteoporosis peripheral skeleton as well as the axial skeleton The term osteoporosis has difficult connota- and cortical bone as well as trabecular bone. tions to the histologist, the radiologist and the Symptoms which may be attributed to the loss clinician; the term now has little practical signi- of bone are most common in the spine and http://pmj.bmj.com/ ficance. Osteoporosis, however defined, is com- routine would suggest that most mon in persons who have not had a stomach bone is lost from the spine. However, all the operation. It is the definition of osteoporosis and measurements of the amount of bone lost with the clinical problem of osteoporosis in the general age show that as much is lost from the peripheral population which I will discuss following Dr skeleton as from the spine. Pulvertaft's paper on osteoporosis after stomach Although subjective assessment of routine operations. radiography of the spine is potentially misleading Osteoporosis was originally defined as the in the individual, the technique has some value on September 28, 2021 by guest. condition of too little bone when the bone which if applied to large numbers of individuals so remained was fully calcified. Thus histological that the errors are randomly distributed. Smith examination of the bone should have been essen- & Rizek (1966) assessed the radiographs of the tial to establish the diagnosis. vertebrae of 1200 normal women, and their The loss of bone may be detected on radio- results show clearly that there is a steady loss of graphs as a lack of calcium but it is difficult to bone from the vertebrae after the age of 45. interpret the radiographs subjectively, and even The factors which reduce the reliability of if lack of calcium is obvious it could be due the routine radiography of the spine are the to osteomalacia or to osteoporosis. unavoidable variations in exposure and develop- In some cases the loss of bone is associated ment of the radiographs and the large and with deformities or fractures of the bones. These variable amount of soft tissue around the spine. E 624 D. B. Morgan Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from Several techniques have been described which frequency of wedge fractures of the spine is give an objective assessment of the amount of greatest in the vertebrae containing least bone bone tissue in the vertebrae (Nordin et al., 1962; (Smith & Rizek, 1966). Oeser & Krokowski, 1963; Hurxthal et al., 1964). Structural failure in the form of wedge frac- However, these techniques lack precision and tures of the spine and fractures of the long they have given most information in epidemio- bones increases in frequency with age and is logical studies. All three studies show a loss of more common in women than men. bone with age; Oeser and Krokowski who were The studies of Meema & Meema (1963) and the only ones to study the bone loss in men and Nordin (1966) show that persons with structural in women found that the loss of bone started failure come from among the persons with least earlier and was more rapid in women than men. bone, but there is no evidence that persons with There are many more data for the changes structural failure form a distinct group with less in the peripheral bone with age, since there is bone than is 'normal' for persons of the same less soft tissue to complicate densitometric tech- age and sex. Thus even the persons with struc- niques and in any case the thickness of the tural failure when considered according to the cortical bone is a simple measure of the amount amount of bone in the skeleton do not form a of bone in the periphery. distinct group with less bone than normal. All these studies show a loss of bone with The most difficult problem is the relation be- age which starts earlier and is more rapid in tween structural failure in the spine and symp- women than men (Meema, 1962; Garn, Rhoh- toms. The expected symptom is backache and man & Nolan, 1964; Nordin, McGregor & Smith, specific characteristics of the backache of spinal 1966; Smith & Rizek, 1966; Morgan et al., osteoporosis have been suggested (Dent & Wat- 1967b). Women lose, on the average, 40-50% of son, 1966). However, backache is no more their bone tissue between the fifth and the ninth common in the elderly than the young or in decades. The obvious suggestion is that the loss women than in men (Nordin et al., 1966; Morgan Protected by copyright. of bone in women follows and may be the result & Pulvertaft, unpublished observations). of the . Meema, Bunker & Meema Also there is no relation between wedge frac- (1965) have obtained some direct evidence to tures and backache even in elderly persons support this suggestion. (Gitman, Kamholtz & Levin, 1958; Smith, Eyler All, or nearly all, persons lose bone as they & Mellinger, 1960). Thus the apparent associa- age, and there is no evidence of a group of tion between backache and fracture of the spine persons who lose more bone than the others and may be explained by the high frequency of both might, therefore, be called 'osteoporotic'. For phenomena which will be commonly associated these reasons the definition of osteoporosis as a although not necessarily casually related. loss of bone tissue is of no value in clinical There are a few patients who have less bone practice. than is 'normal' for their age and sex; these It is, therefore, necessary to restrict the patients are often young men. The fundamental definition in some way. The obvious suggestion abnormality in this condition is not known, http://pmj.bmj.com/ is to confine the term osteoporosis to those but it seems to be different from the disturbance persons where the loss of bone tissue has allowed which to the loss of bone which accom- structural failure. panies aging (Hioco, Miraret & Bordier, 1964). Biconcavity of the vertebral bodies and wedge Cushing's syndrome, thyrotoxicosis and osteo- fractures of the vertebrae have both been taken genesis imperfecta should be considered as causes as evidence of structural failure in the spine. of 'thin bones' at all ages, particularly in the young; True gross biconcavity of the vertebrae as 'thin bones' may be the only sign of Cushing's opposed to apparent biconcavity on radiographs syndrome (Fourman & Thomas, 1964). However, on September 28, 2021 by guest. is rare even in the elderly, probably because all these causes of 'thin bones' are rare compared gross biconcavity will only arise if the interver- with the frequency of 'thin bones' in the elderly. tebral discs retain their turgidity and the inter- As to the treatment of the loss of bone which vertebral discs tend to become less turgid in the accompanies ageing it is clear that the loss can elderly. There is no relation between gross at best be stopped, never corrected. Treatment biconcavity and the amount of bone in the verte- with oestrogens and calcium supplements both brae (Caldwell, 1962; Virtama, Gastrin & Telkka, have strong advocates but it is as yet impossible 1962). Attempts to detect lesser degrees of bicon- to choose between these two means of arresting cavity have failed (Nordin et al., 1966) or have the loss of bone. been abandoned because of lack of precision The therapy of the future may be an attempt (Smith & Rizek, 1966). On the other hand the to prevent the loss of bone by treating some or Osteomalacia and osteoporosis 625 Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from all the patients prophylactically; women from GOUGH, K.R., LLOYD, O.L. & WILLS, M.R. (1964). Nutri- the age of 40 years, men from the age of about tional osteomalacia. Lancet, ii, 1261. Hioco, D., MIRAVET, L. & BORDIER, P. (1964) Bone and Tooth 60 years. (Ed. by H. J. J. Blackwood). Pergamon Press, London. HOBSON, W. & JORDAN, A. (1959) A study of serum alkaline Conclusions phosphatase levels in old people living at home. J. Geront. is a metabolic with 14, 292. Osteomalacia HURXTHAL, L.M., DOTTER, W.E., BAYLINK, D.J. & VOSE, characteristic biochemical, radiological and his- G.P. (1964). Two new methods for the study of osteo- tological features. Unfortunately not all of these porosis and other metabolic bone diseases. Lahey Clin. features need be present in the individual and Bull. 13, 155. few specific for osteomalacia. KLAASEN, C.H.L. & SIERSTSEMA, L.H. (1964) De invloed van of the features are de leeftijd op de alkalische-fosfatase waarde in het serum. For these reasons we believe that a response to Ned. Tijdkr Geneesk. 108, 1433. vitamin D is the essential diagnostic criterion of MEEMA, H.E. (1962) The occurrence of cortical bone atrophy the disease. Osteomalacia is an unusual complica- in and in osteoporosis. J. Can. Ass. Radiol. 13, 27. . When it does happen it MEEMA, H.E. & MEEMA, S. (1963) Measurable roentgenologic tion of gastric changes in some peripheral bones in . is the result of a simple deficiency of vitamin J. Amer. ger. Soc. 11, 1170. D and treatment with small doses of the vitamin MEEMA, H.E., BUNKER, M.L. & MEEMA, S. (1965) Loss of brings early relief of symptoms and heals the compact bone due to menopause. Obstet. Gynaec. 26, 333. MORGAN, D.B., PATERSON, C.R., WOODS, C.G., PULVERTAFT, bones. C.N. & FOURMAN, P. (1965a) Search for osteomalacia in There is no evidence of a distinct disorder of 1228 patients after gastrectomy and other operations on 'osteoporosis' in the elderly other than as one stomach. Lancet, ii, 1085. extreme of the loss of bone which occurs in MORGAN, D.B., PATERSON, C.R., WOODS, C.G., PULVER- all as The are TAFT, C.N. & FOURMAN, P. (1965b) Osteomalacia after persons they age. only exceptions gastrectomy. Lancet, ii, 1089. the rare identifiable causes of 'thin bones' such MORGAN, D.B., LEVER, J.V., PATERSON, C.R., WOODS, C.G., Protected by copyright. as Cushing's syndrome and thyrotoxicosis. PULVERTAFT, C.N. & FOURMAN, P. (1967a) Osteomalacia The loss of bone with age is sometimes asso- (Ed. by D. J. Hioco). Masson et cie, Paris. of and occasion- MORGAN, D.B., SPIERS, F.W., PULVERTAFT, C.N. & FOUR- ciated with fracture the spine MAN, P. (1967b) The amount of bone in the metacarpal and ally with fracture of the long bones. However, the phalanx according to age and sex. Clin. Radiol. 18, 101. there is little relation between fracture of the NASSIM, J., SAVILLE, P., COOK, P., MILLIGAN, G. (1959) The spine and backache, and the syndrome of back- effects ofvitamin D and gluten-free diet in idiopathic steat- fracture of the often be a orrhoea. Quart. J. Med. 28,141. ache and spine may NORDIN, B.E.C. (1966) Medicine in Old Age (Ed. by J. N. chance association of two common happenings Agate), p. 5. Pitman Medical. in the elderly. NORDIN, B.E.C., BARNETT, E., MCGREGOR, J. & NISBET, J. (1962) Lumbar spine densitometry. Brit. med. 1. i, 1793. NORDIN, B.E.C., MCGREGOR, J. & SMITH, D.A. (1966) The References incidence of osteoporosis in elderly women: its relation to ANDERSON, I., CAMPBELL, A.E.R., DUNN, A. & RUNCIMAN, age and the menopause. Quart. J. Med. 35, 25. J.B.M.. (1966) Osteomalacia in elderly women. Scot. med. OESER, H. & KROKOWSKI, E. (1963) Quantitative analysis of

J. 11, 429. inorganic substances in the body. Brit. J. Radiol. 36, 274. http://pmj.bmj.com/ CALDWELL, R.A. (1962) Observations on the incidence, PATERSON, C.R., WOODS, C.G. & MORGAN, D.B. (1968) aetiology and pathology of senile osteoporosis. J. clin. Osteoid in . J. Path. Bact. 95, 449. Path. 15, 421. SMITH, R.W., EYLER, W.R. & MELLINGER, R.C. (1960) On CAMP, J.D. & MCCULLOGH, J.A.L. (1941) Pseudofractures the incidence of senile osteoporosis. Ann. intern. Med. 52, in diseases affecting the skeletal system. . 36, 651. 773. CHALMERS, J., CONACHER, W.D.H., GARDNER, D.L. & ScoTT, SMITH, R.W. & RIZEK, J. (1966) Epidemiologic studies of P.J. (1967) Osteomalacia-a common disease in elderly osteoporosis in women of Puerto Rico and south eastern women. J. Bone Jt Surg. 498, 403. Michigan with special reference to age, race, national DENT, C.E. & WATSON, L. (1966) Osteoporosis. Postgrad. origin and to other related or associated findings. Clin. med. J. Suppl. (October). orthop. 45, 31. on September 28, 2021 by guest. FOURMAN, P. & THOMAS, J.P. (1964) LVOsteoporose (Ed. by STANBURY, S.W. & LUMB, G.A. (1966) Parathyroid function D. J. Hioco), p. 191. Masson et cie, Paris. in chronic renal failure. Quart. J. Med. 35, 1. GARN, M.S., ROHMANN, C.O. & NOLAN, P. (1964) Relations THOMPSON, G.R., NEALE, G., WATTS, J.M. & BOOTH, C.C. of Development and Ageing (Ed. by J. E. Birren). Thomas, (1966) Detection of after partial Springfield, Illinois. gastrectomy. Lancet, i, 623. GITMAN, L., KAMHOLTZ, T. & LEVIN, J. (1958) Osteoporosis VIRTAMA, P., GASTRIN, G. & TELKKA, A. (1962) Biconcavity in the aged: radiographic survey with clinical and bio- of the vertebrae as an estimate of their . Clin. chemical correlations. J. Geront, 13, 43. Radiol. 13, 128.