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Ag e and Ageing (1973), 2, 14
NOR MAL VAL UE S FOR SIXTEEN BLOODC O N S T I T U E N T S IN THE ELDERLYR. G. S. LEASK, G. R. ANDREWS AN D F. I. CAIRD
Department of Biochemistry, Stobhill Hospital, Glasgow and Department ofGeriatric Medicine, University of Glasgow
SummarySixteen common biochemical estimations have been performed on nearly 500 people randomlyselected from those over 65 living at home. The mean values and ranges found for serum sodium,potassium , chloride, bicarbonate, magnesium , bilirubin, inorganic phosp hate, total protein , albumin,and globulin, were identical, and those of urea, creatinine, cholesterol, uric acid, calcium, and alka-line phosphatase were higher than those considered normal in younger people. Sex differenceswere demonstrable for serum urea, creatinine, bilirubin, phosphate, cholesterol, calcium, andalkaline phosphatase; in the Ia3t four instances these seemed likely to be of clinical importance.Biochemical disorders are common in the elderly, and often remediable, but assessmentof their significance may be hampered by lack of precise knowledge of normal values inold age. Both age and sex are known to affect the normal levels of many important andcommonly measured blood constituents (Roberts, 1967; Flynn, 1969; Reed, Cannon,Winkelman, Bhasin, Henry & Pileggi, 1972), but as the subjects in these studies haveusually been blood donors, and thus rarely if ever elderly, any effects of age over 65 yearsmust be determined, if at all, by projection. Attempts to derive normal values for theelderly from data from hospital patients (Pryce, Haslam & Wootton, 1969) are lesslikely to provide convincing results than comparable data from less sick people, such asthe elderly at home.
The present study, which is part of a detailed clinical, laboratory, nutritional, andsocial survey of old people living at home, sets out to provide information on the normalrange of values in old age of sixteen commonly determined blood constituents.
M A T E R I A L AND M E T H O D STwo random samples were drawn from thenames of people aged 6 5 and over living at home. Thefirst (Andrews, Cowan & Anderson, 1971) was from the whole elderly p opulation of the town ofK ilsyth, and the second from six general practices in northe rn Glasgow. Each sample was stratifiedby age so as to increase the proportion of subjects over the age of 75 from approximately one inthree to about one in two. About 25 per cent of those who were approached refused to participate.Subjects acutely ill at the time they were approached were excluded. The Kilsyth survey con-tinued until 201, and the Glasgow survey until 300 subjects had taken part.A full clinical history, including details of drugs currently being taken, was obtained, and aphysical examination carried out. Blood was taken by venepuncture, a tourniquet being used ifnecessary, at approximately 11 ajn. in the case of the majority of the Kilsyth subjects, and at1.30 p.m. in the case of the Glasgow subjects.
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Normal Values for Sixteen Blood Constituents in the Elderly 15The analytical methods used are shown in Table I. The results from the Kilsyth and Glasgowsubjects were essentially the same, andhave been combined for the purposes of analysis. Cumula-tive frequency distributions for each constituent were plotted onprobability paper to determine
their nature. The distributions found are shown in Table I, together with those given by others(W ootton & King, 1953; Roberts, 1967). Subjects currently taking benzothiadiazines or otherdiuretics were excluded from the calculation for several cons tituents (see Table I).Table I. Analytical methods used, and type of frequency distribution found
Distribution foundW ootton& King(1953)
NLNNNNNNNN SLLLLL
Roberts(1959)NNNNNNNNNNLLLL
ThisStudyNNNNNNNNNNNLLLLL
Constituent MethodSodiunrf Technicon* AutoAnalyzer* Methodology N- 21b /IPotassiumf Technicon AutoAnalyzer Methodology N- 21b /IChloridef Technicon AutoAnalyzer Methodology N- 21b /IBicarbo natef Techn icon AutoA nalyzer Meth odology N21b/ICalcium Technicon AutoAnalyzer Methodology N-3bPhospha te Young (1966)Magnes ium Orange & Rhein (1951)Uri c Acidf Crowley (1964)Tota l Protein Technicon AutoAnalyzer Methodology N- 14bAlbumin Northam & W iddowson (1967)Globulin Difference between Tota l Protein and AlbuminUrea f Technicon AutoAnalyzer Methodology NlcCreatininef Technicon AutoAnalyzer Mediodology N - l l bBilirubin Technicon AutoAnalyzer Methodology N12aAlkalinephosphatase Axelsson, Ekman & K nutsson (1965)Cholesterol Annan & Isherwood (1969)
N = norm al; L = lognormal; NS = negative skew; = not done. Technicon and AutoAnalyzer are registered trade marks of Technicon Instruments CompanyLtd., Hamilton Close, Houndsmills, Basingstoke, Hants.f Subjects taking thiazides or other diuretics excluded from analysis for these constituents.R E S U L T S
These results are shown in Tables II to VII, as means and standard deviations in thecase of contituents with a normal distribution, and as logarithmic means and 95 per centranges in the case of those with a lognormal distribution. The subjects are divided bysex, and by age under or over 75.
There was no trend with age nor any sex difference in the concentrations of sodium,potassium, chloride or bicarbonate (Table II). The mean values ( S.D.) are 140-8 2-8, 4-4 04, 102-4 2-9 and 25-1 2-8 mmol/litre respectively.
Mean values for serum calcium concentration, both uncorrected and corrected forserum protein concentration (Dent, 1962) fell with age, being approximately 0-2 mg/100ml lower in both sexes in those over 75 than in those under that age. They were higher,by 0-16-0-19 mg/100 ml, in women than in men. The serum calcium concentration wasover 10-5 mg/100 ml in 17 women (5-7 per cent) and 5 men (2-9 per cent). The corre-sponding figures for corrected serum calcium concentration were 15 (5-0 per cent) and 4
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Na+ (mmol/litre)K+ (mmol/litre)Cl~ (mmol/litre)HCO3 (mmol/litre)
No.
Table II. Electrolytes (mean S.D.; distributions normal)Se xAg eN o .
65-7495
M75 +
6865-74
149
F75 +
133
M65 +
16 3
F65 +
27 8
M + F65 +
44 1140-53-l
4-50-41021 3 025 3 2 8
140-82-54-50-3
102-72-825-72-6
141-0264'40-4
102-42-92 5 - 3 3 O
1 4 0 9 3 04 - 3 0 - 4102-53-024-82-5
1 4 0 6 2 - 94-50-3102-63-025 -2 2-7
140-92-84-40-4102-42-92 5 1 2-898 74 159 142 17 2 30 1
Ca++ (mg/100 ml)CorrCa++ (mg/100 ml)PO 4 (mg P/100 ml)
9-640-45 9-440'37 9-800-50 9-630-569'560-482-980-52 9-420-402-990-47 9-740-513-410-57 9-560-583-35O-63 3O6 0-49 3-390-60
14O-82-84-40-4102-42-925 1 2-8 I9
Corr. Ca++ = serum calcium corrected for total protein concentration.
Table III. Plasma proteins (mean S.D.: distributions normal)Se xAg eN o .
Total protein (g/100 ml)Albumin (g/100 ml)Globulin (g/100 ml)743
65-7498
13 0-04 0-16 0-
M
494156743
75+77
07 007 005 0596756
742
65-7415 8
13 0160960-
I
474244
F
742
75 +15 0
060150990
483952
743
M65 +
175100040100
534156742
F65 +
30 8090150990
484048743
M + F65 +
48 3100-11 0-05 0-
504153
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Norm al V alues for Sixteen Blood Constituents in the Elderly 17(2-3 per cent). Serum calcium concentrations of 11-0 mg/100 ml or more were found in8 women and 1 man. Mean values for serum inorganic phosphate concentration wereunaffected by age, but were higher in wom en (3-39 + 0-60 mg P/100 ml) than in men( 3 - 0 60 4 9 m g P /1 0 0 m l ) .Mean values for total plasma proteins fell slightly with age, being 0-06-0-07 g/100 mllower in those over than in those under 75 (Table III). There was no sex difference intotal plasma protein concentration, but the mean serum albumin concentration was0-11 g/100 ml higher in women, and the mean serum globulin concentration higher, bythe same amount, in men.The logarithmic means of serum urea and creatinine concentrations were higher inmen than women, and rose with age in both sexes (Table IV). Upper 95 per cent limitsfor serum urea concentration were approximately 6 0 mg/100 ml, and for serum creatinine,1-9 mg/100 ml.Serum bilirubin concentrations showed no trend with age, but the logarithmic meanwas 01 mg/100 ml higher in men than women (Table IV). The upper 95 per cent limitTable IV. Serum urea, creatinine, bilirubin and alkaline phosphatase (log meanS.D. ; meanand 95 per cent range; distributions lognormal)SexAgeUrea (mg/\00 ml)N o .Log meanS.D.Mean95 % rangeCreatinine(mg/100 ml)N o .Log meanS.D.Mean95 % rangeBilirubin(mg/100 ml)N o .Log meanS.D.Mean95 % rangeAlkalinephosphatase(K-A units)N o .Log meanS.D.Mean95 % range
65-74951-5845+ 0-095938-425-60
860-0384 0 1 0 9 01-090-66-1-8195T-82640-17670-670-30-1-51
940-99920-15491 0 05-20
M75 +
6 91-6301+ 0-098542-727-67
610 07740-09341-200-78-1-8473T-82830-14980-670-34-1-34
781-0242+ 0-124710-66-20
65-7414 91-54240-102734-922-60
140T-9615 0 1 6 4 60-910-43-1-9514 61-7469 0 1 6 1 80-560 - 2 6 - 1 1 8
16 4103960-14541 1 06-21
F75 +
13 41-5625. 0 1 1 0 236-522-61
1180 0 1 8 10-08971 0 40-44-1-58137T-74640-14770-560-28-1 10
14 31 0 9 5 0 0 168012-56-27
M65+
168T-8244 0 1 6 8 90-670-31-1-46
17210119+ 0 1 4 6110-35-20
F65 +
2831-74720-15510-560-27-1-14
3071-06590-158411 -66-24
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Norma l Values for Sixteen Blood Constituents in the Elderly 19D I S C U S S I O N
Assessment of the significance of the findings in a study such as this necessitates dis-cussion of the problems of sampling and of technical and statistical methodology. Therecan be no d oubt that a sample of old people living at hom e is more likely to approximateto the ad mittedly somewhat hypothetical concept of 'normal old age* than one draw nfrom elderly hospital patients. In the present study the acutely ill were excluded, andthough abnormalities were detectable on clinical examination or simple investigation inevery subject, it seems unlikely that (with one exception) any one abnormality w ould b efrequent enough to bias the results of more than one blood constituent investigated.Th e exception is the taking of oral diuretics, which m ight be expected to affect the re sultsin at least the cases of serum sodium, potassium, chloride, bicarbonate, urea, creatinine,and uric acid. Subjects taking diuretics were therefore excluded from the analysis of theresults for these constituents. Little bias is likely to have been introduced by th e relativelyhigh rate of refusal to participate, since Akhtar (1972) found that the physical health (onsuperficial examination) of the Kilsyth subjects who refused to take part was good. In asimilar survey, with a similar refusal rate, M ilne, M aule & W illiamson (1971) reportedsimilar conclusions.The principal technical problems encountered derive from the fact that the bloodsamples were not taken in the fasting state, and from the need to use a tourniquet toobtain adequate blood samples (of 50 ml) from a number of subjects. Food may lowerserum inorganic phosphate concentration (Annino & Relman, 1959). Venous stasis,particularly if accompanied by forearm exercise, is known to affect levels of sodium,potassium, chloride, calcium, protein, and cholesterol (Broome & Holt, 1964), but themean values of these constituents found in this stu dy are close to those found both whenvenous stasis was excluded (Flynn, 1969) and when it was employed (Roberts, 1967).A tourniquet is often needed in clinical practice, and its effects, except perhaps in thecase of serum calcium, are relatively small and customarily disregarded.
Dispute and difficulty surrounds the proper statistical presentation of biochemicalresults (Roberts, 1967; Reed, Henry & Mason, 1971), but it would seem as a minimumessential to determine the type of frequency distribution for each constituent. Table Ishows that this study is in excellent general agreement on this point with previousfindings (W ootton & K ing, 195 3; Robe rts, 1967). Th e findings for those con stituentswhose frequency distribution is normal have been presented in the conventional way, asthe mean and standard deviation, from which the 95 per cent range can be easilydeterm ined. Constituents w hose distribution is lognormal are shown as the logarithmicmean and the upper and lower limits of the 95 per cent range, because it is usually thisrange with which the clinician is concerned.The mean values and standard deviations found in the present study for many bloodconstituents (e.g. serum sodium, potassium, chloride, bicarbonate, magnesium) show novariation with age or sex, and are very close to those found by others in middle age(W ootton & Kin g, 195 3; Roberts, 1967; Flyn n, 1969) and those quoted in textbooks(Cantarow & Tru mp er, 1963). Chen & Millard (1972) found 5 5 per cent of serumsodium concentrations in old people at home to be below 137 mequiv/litre. Subjectstaking oral diuretics were not excluded, but the explanation of this high frequency ofhyponatraemia is obscure. It may be concluded both that age pe r se has no major effect
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20 . R. G. S. Leask, G. R. Andrews and F. I. Cahdupon the blood levels of these constituents, and also that 'abnormal' levels are notcommonly encountered in relatively healthy old people.The sex difference in serum bilirubin concentrations has been noted by others(O'Hagan, Hamilton, Le Breton & Shaw, 1957; Reed et al., 1972), but is not largeenough to have clinical significance. It does not appear to be due to any difference in theprevalence of frank liver disease, since any other evidence of liver disease was very rarein the population studied. The upper limits found for bilirubin concentration are abovethose commonly given (0-9-10 mg/100 ml). Some of the subjects with levels of1-1 mg/100 m l and more may have been examples of constitutional hyperbilirub in-aemia (Gilbert's syndrome).Serum calcium levels have been shown to fall with age, but to be higher in post-menopausal women than in men of the same age (Young & Nordin, 1967; Flynn, 1969;Reed et al., 1972). They rise after oophorectomy and fall with the administration ofoestrogens (Young, Jasani, Smith & Nordin, 1968; Riggs, Jowsey, Kelly, Jones &Maher, 1969). These phenomena have been attributed to the withdrawal of oestrogenicinfluences on the skeleton at the menopause and the development of a state of relativehyperparathyroidism (Hossain, Smith & Nordin, 1970). The fact that serum inorganicphosp hate levels are higher in older women th an in men (Greenberg, W inters andGraham, I960; Reed et al, 1972) (Table II) is difficult to reconcile with this hypothesis,but whatever the mechanism and significance of the sex difference in serum calciumconcentrations, in the present study a substantial proportion of women (5-7 per cent)were found to have levels above the commonly accepted upper normal limits of 10-5mg/100 ml. This proportion is little affected by correction for serum protein concentra-tion. Some of these high values may perhaps be due to venous stasis and some to bloodsamples being taken in the non-fasting state. Certainly it is difficult to believe that thepopulation prevalence of hyperparathyroidism or any other cause of hypercalcaemia canbe as great as 5 per cent. None of the subjects with high serum calcium concentrationswas investigated in further detail, but none had any symptoms or radiological or otherbiochemical evidence of hyperparathyroidism. The"true upper limit for normal serumcalcium concentration in women over 60 may in fact be as high as 11-4 mg/100 ml(Reed et al., 1972).Age-related changes in serum alkaline ph osphatase levels are well described (Clark,Beck & Shock, 1959; Hobson & Jordan, 1959). Th e increase with age is sometimesattributed to an increasing prevalence of occult Paget's disease of bone, but this isunlikely to explain the sex difference, which has also been previously demonstrated(Hobson & Jordan, 1959; Roberts, 1967), since the serum alkaline phosphatase level ishigher in women at all ages, while Paget's disease is generally considered commoner inmen. It is possible that the high values in old age, and especially in old women, aredue to a considerable prevalence of unrecognized osteomalacia due to dietary VitaminD deficiency (Exton-S mith, Hodkinson & Stanton , 1966; Chen & Millard, 1972). Th eremay b e some correlation in elderly, women between high serum alkaline ph osphatase
levels and subnormal Vitamin D intake (McLennan, Caird & Macleod, 1972). However,values up to 20 K-A units per 100 ml can probably be accepted as normal in elderlywomen (Reed et al., 1972).Sex differences and an age-related increase in serum urea and creatinine are welldescribed in middle age (Campbell, Greene, K eyser, W aters, W eddell & W ithey, 1968;
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Norma l Values for Sixteen Blood Constituents in the Elderly 21K aufman, Gran t & Moo rhouse, 1969, W aters, Elwood, Asscher & Abe me thy, 1970)and have also been shown in old age (Milne & W illiamson, 1972). Th e sex difference istoo small to be of practical importance, but the upper 95 per cent limit, shown in TableIV, of approximately 60 mg/100 ml for serum urea concentration is in agreement withthe findings of Milne & W illiamson (1972), and also with clinical experience, that inold age values between the customary upper limit of normal of 40 mg/100 ml and 60mg/100 ml do not signify renal failure. The increase with age in blood levels of thesetwo substances which are both very largely excreted by glomerular filtration undoub tedlyreflects the well-described fall with age in glomerular filtration rate (Shock, 1968), ormore precisely, the fact that this fall exceeds any age-related fall in output of urea orcreatinine.A sex difference and age-related rise in serum uric acid concentration is well estab-lished (Dodge & Mikkelsen, 1970; Reed et al., 1972). In the present study, exclusion ofsubjects taking oral diuretics proved important in this connection, since the serum uricacid level was over 8 mg/100 ml in 11 of29 such subjects, and over lOmg/lOOmlin 5. Nosubjects were encountered in whom a diagnosis of gout was justified. This study suggeststhat in the elderly the upper limit of normal using the method of Crowley (1964) shouldbe taken as approximately 7-7 mg/100 ml in both sexes.T he m ean values for total plasma prote in shown in Table I II are little different fromthose found by others in middle age (W ootton & K ing, 195 3; Roberts, 1967), and do notsupport the view that there is a substantial decline with age in plasma protein levels(Pryce et al., 1969; Reed et al., 1972). The sex differences found, of higher serumalbumin levels in women and of globulin in m en, are not large, but do not appear to havebeen noted previously, and are difficult to explain.The serum cholesterol level in any population is undoubtedly affected both by ageand sex, and by other factors probably mainly nutritional in origin (Keys, 1957). It iswell established that serum cholesterol levels show an increase with age in both sexes andan additional increase in women after the menopause, so that levels are higher in menthan women under the age of 50 and higher in women over that age (Adlersberg,Schaefer, Steinberg & W ang, 195 6; Reed et al., 1972). The findings in the presentinvestigation support this view, though they show a slight fall with age over 75 in bothsexes, such as might result from a cohort effect due to the earlier death of people withhigher cholesterol levels. The absolute values found in the present study are high, withover 40 per cent of women and 8 per cent of men having a serum cholesterol concentrationover 300 mg/100 ml, but are very similar to those found by others (Hobson, Jordan &Roseman, 1953; Reed et al., 1972). There is no evidence that the high values in womenreflect the existence of a large pool of subjects with undiagnosed hypothyroidism(Tho ms on, Andrews, Caird & W ilson, 1972).In summary, the present study shows that the blood levels of many commonly deter-mined constituents are identical in the elderly to those well known in youth and middleage. Abnormal values of these constituents must therefore be considered abnormalregardless of age. In other instances, such as serum urea, creatinine, uric acid andcholesterol, values in healthy old people may differ substantially from those in middleage. Values within the ranges demonstrated should therefore not give rise to concern inold people, nor should they result in unnecessary, inconvenient, and possibly evenhazardous investigations. Sex differences can be shown in old age for the blood levels of
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22 R. G. S. Leask, G. R. Andrews and F. I. Cairdmany substances, but are only rarely of a magnitude sufficient to make them of clinicalsignificance.
A C K N O W L E D G E M E N T SOur thanks are due to the general practitioners in Kilsyth and northern Glasgow forpermission to study their patients, to our colleagues in the surveys, in particular DrsA. J. Akhtar, A. J. J. Gilmore and W. J. McLennan, Miss A. C. Crombie, S.R.N., andMiss J. MacDougall, S.R.N.; to Dr J. W. Chambers and the staff of the BiochemistryDepartment, Stobhill Hospital, for the estimations; and to the subjects for their willingco-operation. The study was supported by a grant from the Nuffield Provincial HospitalsTrust.
REFERENCESADLERSBERC, D., SCHAEFER, L. E., STEINBERG, A. G. & W A N G , C. I. (1956). Age, sex, serumlipids in coronary atherosclerosis. Jf. Am. med. Ass. 162, 619.AKHTAR, A. J. (1972). Refusal to participate in a survey of the elderly. Geront. Clin. In the press.ANDREWS, G. R., C O W A N , N. R. & ANDERSON, W. F. (1971). The practice of geriatric medicinein the community. In: Problems and Progress in Medical Care. Essays on Current Research,5th Series, ed. McLachlan, G. p. 58. Oxford: U niversity Press.ANNAN, W. & ISHERWOOD, D. M. (1969). An automated method for the direct determination oftotal serum cholesterol. J. med. Lab. Tech. 26 , 202.A N N IN O , J. S. & RELMAN, A. S. (1959). The effect of eating on some of the clinically importantchemical constituents of the blood. Am . J. clin. Path. 31, 155.AXELSSON, H., E K M A N , B. & KNUTSSON, D. (1965). In: Automation in Analytical Chemistry, ed.Skegjjs, L. T., p. 603. Technicon Symposia.BROOME, T. P. & H O L T , J. M. (1964). Venous stasis and forearm exercise during venepuncture assources of error in plasma electrolyte determinations. Can. med. Ass. J. 90, 1105.CAMPBELL, H., GREENE, W. J. W., KEYSER, J. W., WATERS, W. E., WEDDELL, J. M. & WIT HE Y, J. L.(1968). Pilot survey of haemoglobin and plasma urea concentration in a random sample ofadults in W ales 1965-1966. Br.J. prev. soc. Med. 22, 41.CANTAHOW, A. & TRUMPER, M. (1963). Clinical Biochemistry. 6th edn. Philadelphia and London:Saunders.CHE N, F. W. K. & MILLARD, P. H. (1972). The effect of ageing on certain biochemical values.Modern Geriatrics, 2, 92.CLARK, L. C, BE CK, E. I. & SHOCK, N . W . (1959). Serum alkaline phosphatase in middle and oldage. J. Geront. 6, 7.CROWLEY, L. V. (1964). Determination of uric acid: an automated analysis based on a carbonatemethod. Clin. Chem. 10, 838.D E N T , C. E. (1962). Some problems of hyperparathyroidism. Br. med. J. 2, 1419.D O D G E, H. J. & MIKKELSEN, W. M. (1970). Observations on the distribution of serum uric acidlevels in participants of the Tecumseh, Michigan, Community Health studies. J. Chron. Dis.23, 161.FJCTON-SMTTH, HODKINSON, H. M. & STANTON, B. R. (1966). Nutrition and metabolic bonedisease in old age. Lancet, ii, 999.FLYNN, F. V. (1969). Effect of age and sex on the normal range. Ann. clin. Biochem. 6, 1.GREENBERG, B. G., WrNTERS, R. W . & GRAHAM, J. B. (1960). The normal range of plasma phos-phorus and its utility as a discriminant in the diagnosis of congenital hypophosphataemia. J.din. Endocr. Metab. 20, 364.
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Normal Values for Sixteen Blood Constituents in the Elderly 23HOBSON, W . & JORDAN, A. (1959). A study of serum alkaline phosphatase levels in old peopleliving at home. J. Geront. 14, 292.HOBSON, W ., JORDAN, A. & ROSEMAN, C. (1953). Serum cholesterol levels in elderly people living
at home. Lancet, ii, 961 .HOSSAIN, M ., S MI TH, D. A. & NORDIN, B. E. C. (1970). Parathyroid activity and post-menopausalosteoporosis. Lancet, i, 809.KAUFMAN, B. J., GRANT, D. R. & MOORHOUSE, J. A. (1969). An analysis of blood urea nitrogenand haemoglobin values in a population screened for diabetes mellitus. Can. med. Ass. J. 100,744.KEYS , A. (1957). Diet and the epidemiology of coronary heart disease. J . am . med. Ass. 164, 1912.MCLENNAN, W . J.F CAIRD, F. I. & MACLEOD, C. (1972). Diet and bone rarefaction in old age.Age and Ageing, 1, 131.M I L N E , J. S., MAULE, M. M. & W ILLIAMSON, J. (1971). Method of sampling in a study of olderpeople with a comparison of respondents and non-respondents. Br . J. prev. soc. M ed. 25, 37.M I L N E , J. S. & W ILLIAMSON, J. (1972). Plasma urea concentration in older people. Geront. Clin.14, 32 .NORTHAM, B. E. & WI DDOWS ON, G. M. (1967). A.C.B. Technical Bulletin No. 11.O'HAGAN, J. E.( HAMILTON, T ., LE BRETON, E. G. & S HAW, A. E. (1957). Human serum bilirubin.Clin. Chem. 3, 609.ORANGE, M . & RHEI N, H. C. (1951). Micro-estimation of magnesium in body fluids. J . biol. Chem.189, 379.PRYCE, J. D ., HASLAM, R. M. & WOOTTON, I. D. P. (1969). Extraction of normal values from amixed hospital population. Ann. din. Biochem. 6, 6.REED, A. H., CANNON, D. C, WI NKELMAN, J. W., BHASIN, Y. P., HENRY, P. J. & PILECGI, V. J.(1972). Estimation of normal ranges from a controlled sample survey. Sex- and age-relatedinfluences on the SMA 12/60 screening group of tests. Clin. Chem. 18, 57.REED, A. H., HENRY, R. J. & MASON, W . B. (1971). Influence of statistical method used on theresulting estimate of the normal range. Clin. Chem. 17, 275.RIGGS, B. L., JOWSEY, J., KELLY, P. J., JONES, J. D. & MAHER, F. T. (1969). Effects of sex hor-mones on bone in primary osteoporosis. J. clin. Invest. 48 , 1065.ROBERTS, L. B. (1967). The normal ranges, with statistical analysis, for seventeen blood constitu-ents. Clin. Mm . acta 16, 6 9.SHOCK, N . W . (1968). Physiology of ageing. In : Surgery of the Aged and Debilitated Patient, ed .Powers, J. H., p. 10. Philadelphia and London: Saunders.THOMSON, J. A., ANDREWS, G. R., CAIRD, F . I. & W I L S O N , R. (1972). Serum protein-bound andplasma inorganic iodine in the elderly at home. Age and Ageing, 1, 158.WATERS, W . E., ELWOOD, P. C , ASSCHER, A. W . & ABERNETHY, M. (1970). Clinical significanceof dyauria in women. Br . med. J . 2, 754.WOOTTON, I. D. P. & K I N G , E. J. (1953). Normal values for blood constituents: inter-hospitaldifferences. Lancet, i, 470.YOUNG, D. S. (1966). Improved method for the automatic determination of serum inorganicphosphate. J. din. Path. 19, 397.YOUNG, M. M., JASANI, C, S MI TH, D. A. & NORDIN, B. E. C. (1968). Some effects of ethinyloestradiol on calcium and phosphate metabolism in osteoporosis. Clin. Sci. 34, 411.YOUNG, M. M. & NORDIN, B. E. C. (1967). Effects of natural and artificial menopause on plasmaand urinary calcium and phosphate. Lancet, ii, 118.
Address for reprints:F. I. Caird, University Department of Geriatric Medicine, Southern General Hospital, GlasgowG51 47T.
