Scand J Rheumatology 4: 73-79, 1975
BONE LOSS IN PATIENTS WITH RHEUMATOID ARTHRITIS A. C. Kennedy,', D. A. Smith,2,W. W. Buchanan,' J. B. AndersonZand M. K. Jasani
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 10/26/14 For personal use only.
From 'The Centre for Rheumatic Diseases, University Department of Medicine, Royal Injirmary, Glasgow, and 'The Bone Metabolism Research Unit, University Department of Medicine, Western Infirmary, Glasgow , Scotland
ABSTRACT. Both male and female patients with rheumatoid arthritis show a significant bone loss in the femur, compared with the Iw of bone seen in normal subjects with increasing age. A very similar pattern is seen in corticosteroid treated patients with rheumatoid arthritis. There is no evidence to suggest that the corticosterdd therapy has caused a greaterloss of bone from the femur than would have occurred as a result d the rheumatoid arthritis alone. There was a statistically signiecant relation between the duration of the rheumatoid arthritis and femoral bone loss in women over the age of 45 years, whether or not they had been given steroid therapy. There wax also a significant relation between femoral bone lw and the duration of corticosteroid therapy in both male and female patients over 45 years of age, but again it appears unlikely that corticosteroid therapy had contributed Significantly to the femoral bone loss. The Metacarpal and Femoral Indices of the patients were signlfkantly related in both male and female groups. Localised loss of bone in association with rheumatoid arthritis (RA) is widely recognised (3, 11, 2). The cause of the bone loss is uncertain, but could be associated with relative immobility in the region of the joints, and it could also be affected by the generalised inflammatory nature of the disease. Relatively few quantitative measurements of bone loss have been related to the duration of the disease, and the effects of age, sex and steroid therapy. We have described the quantitative bone loss found in the metacarpal (9,as measured by the Metacarpal Index (I). The small joints of the hands and wrist are severely affected in RA, and local factors play an important role in the loss of bone from the metacarpal. The object of the present study was to examine the effects at the midpoint of the femur, which site would be less affected by local joint changes, and to relate these effects to the duration of the disease and the effects of steroid therapy .
MATERIAL AND METHODS The method used for measuring changes in bone mass was that described by Barnett & Nordin (I). X-rays of the left femur and right second metacarpal were taken, the thigh and hand being placed in contact with the film, at a film focal distance of 100 cm. The internal and external diameters of the bone at the midpoint were measured with a Vernier caliper. The femoral and metacarpal indices were obtained by dividing the sum of the cortical widths by the external diameter so as to allow for differences in size, in order that direct comparisons could be made, for example, between male and female patients.
Subjects studied Three hundred and sixty-one patients with rheumatoid arthritis were studied. The definition of RA was that proposed by The American Rheumatism Association (9). Two hundred and one female patients, and 150 male patients were examined. Seventy of the female patients, and 24 of the male patients had received oral steroids (Table I). The results obtained from these groups were compared with those obtained in normal subjects. The normal subjects comprised 119 female, and 76 male controls. These subjects were obtained by approaching the relatives and friends of patients in the general and medical wards of the Western Infirmary, Glasgow, to enquire if they would be willing to have an X-ray of their metacarpal and femur taken. The scope and reason for the investigation was fully explained to them, and at the same time a standard questionnaire was completed to ensure that there was no history of disease that might affect bone mass. The control subjects have been studied elsewhere and the results reported in (10).
RESULTS The results of the analysis of the clinical and diagnostic criteria are shown in Table I. These are shown as the mean and 1 S.D. in each patient group. The mean age of the male patients was significantly greater than that of the female patients. This difference was still apparent after subdividing them into Scand J Rheumatology 4
74
A . C . Kennedy et al.
Table I. Clinical arid diagnostic fentiires i n male and fernole patients with rheumatoid arthritis Female patients
Male patients Non-steroid treated A
A+B
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 10/26/14 For personal use only.
~
Steroid treated B
Non-steroid Steroid treated treated A B
A'+B'
~
71 130 I50 126 24 20 1 48.9f1 1.9 52.1f28.4 59.9f13.0 50.32123 5 7 . l f l l . O 56.lf11.7 8.9f6.2 6.8f9.2 15.0f10.5 7.8f10.7 12.7f13.4 12.6k9.0 228.0f506.7 144.6f590.0 264.7f283.4 226.7k530.0 1%.4f395.0 312.5f634.6 45.3 f 6 . 7 45.6k4.1 45.4k6.2 3.31k0.8 3.24k0.42 3.44k0.59 3.28f0.44 3.54f0.51 3.62f0.5 3.54f0.75 3.54f0.69 334f0.72 3.69 f0.85 3.6720.74 3.68k0.88
Numbers Age (years) Duration of arthritis (years) Rheumatoid Factor titre Age at menopause (years) Serum albumin (sit) Serum globulin (g/l) Erythrocyte Sedimentation Rate Haemaglobtn concentration (g/100 mi)
47.9k29.1
46.21t28.0
50.8k28.2
48.4f30.4
46.0530.1
49.2f30.7
13.8k1.8
13.9f1.8
13.6f1.9
12.lf1.7
12.4f 1.8
12.0f2.4
corticosteroid treated (CT) and non-corticosteroid treated (N-CT) groups, the male patients being significantly older than the female patients. There was no significant difference in age between the CT and N-CT male patients or between the C T and N-CT female patients. A similar pattern emerged when considering the duration of the arthritis which was, on average, present for longer in the male than in the female subjects. The mean titre of rheumatoid factor was higher in both the male and female C T groups than in the N-CT patients, though these differences did not reach statistical significance. In the female patients, the age of onset of the menopause was almost identical in the CTand N-CT groups. The mean serum albumin and globulin levels were slightly. but not significantly, higher in the male patients. The mean erythrocyte sedimentation rate was not significantly different in any of the groups.
The male patients had a significantly higher haemoglobin level than the female patients in all three groups. However, there was no significant difference between the C T and N-CT male patients and this was also true for the CT and N-CT female patients. Bone loss is well-known to occur in both male and female subjects with increasing age, as measured by the Femoral Index (7, 10). The femoral indices in the patient groups have therefore been compared by decades with the control subjects. In Fig. 1, the femoral indices of the noncorticosteroid treated fernale patient group is seen to be significantly lower than those of the control subjects in each decade between 25 and 74 years of age. In the female CT group, the femoral indices were significantly lower than in the normal subjects in all age groups, except in the decade 25 to 34 years of age (Fig. 2). When the
70
70
1
1
f
I
E
RMAlE
El
FEMORAL INDEX x)
,
0.001
P'D(DI
,
P~oo(11
,
PIwol
,
Paw!
,
I Normd
B
*A
25
0
25
35
45
55
65
n
AGE-)aon
Fig. I . The mean and Standard Error of the Femoral Index
are shown by decades in normal female subjects, and in female patients with RA. Scand J Rheumatologj 4
i5
15
if
65
A
AGE - m N
Fig. 2. The mean and Standard Error of the Femoral Index
are shown by decades in normal female subjects and in female patients with RA who have been treated with corticosteroids.
70
-
50-
FEMALE FEMORAL INDEX 3o
70
'
'
1 NS
NS
NS
NS
50
1
--
'
p
B
*
NS
NS
I
R.A.
I
NOtrnd
fl
R.A-Sl.roidTnhd
E
R*
I
femoral indices in the CT and N-CT groups were compared (Fig. 3), the C T groups at each decade had marginally lower mean values, but in no decade did this reach statistical significance. In the male patients who had not been treated with corticosteroids, the mean femoral indices were all lower than those of the control subjects in each decade between 25 and 74 years of age (Fig. 4), but only reached statistical significance between 45 and 64 years. The number of male patients who were treated with corticosteroids was small (twenty-four), one patient was below 45 years of age, and the rest ranged between 45 and 74 years of age. The mean values were lower in each of the three decades, compared with the control subjects, but only reached statistical significance in the 55 to 64 year age group (Fig. 5). When the CT male patients with RA were compared with the N-CT group in the three
0
1
I El
El
MALE FEMORAL INDEXJo
NS
0
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 10/26/14 For personal use only.
-.
P
BONE LOSS IN PATIENTS WITH RHEUMATOID ARTHRITIS A. C. Kennedy,', D. A. Smith,2,W. W. Buchanan,' J. B. AndersonZand M. K. Jasani
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 10/26/14 For personal use only.
From 'The Centre for Rheumatic Diseases, University Department of Medicine, Royal Injirmary, Glasgow, and 'The Bone Metabolism Research Unit, University Department of Medicine, Western Infirmary, Glasgow , Scotland
ABSTRACT. Both male and female patients with rheumatoid arthritis show a significant bone loss in the femur, compared with the Iw of bone seen in normal subjects with increasing age. A very similar pattern is seen in corticosteroid treated patients with rheumatoid arthritis. There is no evidence to suggest that the corticosterdd therapy has caused a greaterloss of bone from the femur than would have occurred as a result d the rheumatoid arthritis alone. There was a statistically signiecant relation between the duration of the rheumatoid arthritis and femoral bone loss in women over the age of 45 years, whether or not they had been given steroid therapy. There wax also a significant relation between femoral bone lw and the duration of corticosteroid therapy in both male and female patients over 45 years of age, but again it appears unlikely that corticosteroid therapy had contributed Significantly to the femoral bone loss. The Metacarpal and Femoral Indices of the patients were signlfkantly related in both male and female groups. Localised loss of bone in association with rheumatoid arthritis (RA) is widely recognised (3, 11, 2). The cause of the bone loss is uncertain, but could be associated with relative immobility in the region of the joints, and it could also be affected by the generalised inflammatory nature of the disease. Relatively few quantitative measurements of bone loss have been related to the duration of the disease, and the effects of age, sex and steroid therapy. We have described the quantitative bone loss found in the metacarpal (9,as measured by the Metacarpal Index (I). The small joints of the hands and wrist are severely affected in RA, and local factors play an important role in the loss of bone from the metacarpal. The object of the present study was to examine the effects at the midpoint of the femur, which site would be less affected by local joint changes, and to relate these effects to the duration of the disease and the effects of steroid therapy .
MATERIAL AND METHODS The method used for measuring changes in bone mass was that described by Barnett & Nordin (I). X-rays of the left femur and right second metacarpal were taken, the thigh and hand being placed in contact with the film, at a film focal distance of 100 cm. The internal and external diameters of the bone at the midpoint were measured with a Vernier caliper. The femoral and metacarpal indices were obtained by dividing the sum of the cortical widths by the external diameter so as to allow for differences in size, in order that direct comparisons could be made, for example, between male and female patients.
Subjects studied Three hundred and sixty-one patients with rheumatoid arthritis were studied. The definition of RA was that proposed by The American Rheumatism Association (9). Two hundred and one female patients, and 150 male patients were examined. Seventy of the female patients, and 24 of the male patients had received oral steroids (Table I). The results obtained from these groups were compared with those obtained in normal subjects. The normal subjects comprised 119 female, and 76 male controls. These subjects were obtained by approaching the relatives and friends of patients in the general and medical wards of the Western Infirmary, Glasgow, to enquire if they would be willing to have an X-ray of their metacarpal and femur taken. The scope and reason for the investigation was fully explained to them, and at the same time a standard questionnaire was completed to ensure that there was no history of disease that might affect bone mass. The control subjects have been studied elsewhere and the results reported in (10).
RESULTS The results of the analysis of the clinical and diagnostic criteria are shown in Table I. These are shown as the mean and 1 S.D. in each patient group. The mean age of the male patients was significantly greater than that of the female patients. This difference was still apparent after subdividing them into Scand J Rheumatology 4
74
A . C . Kennedy et al.
Table I. Clinical arid diagnostic fentiires i n male and fernole patients with rheumatoid arthritis Female patients
Male patients Non-steroid treated A
A+B
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 10/26/14 For personal use only.
~
Steroid treated B
Non-steroid Steroid treated treated A B
A'+B'
~
71 130 I50 126 24 20 1 48.9f1 1.9 52.1f28.4 59.9f13.0 50.32123 5 7 . l f l l . O 56.lf11.7 8.9f6.2 6.8f9.2 15.0f10.5 7.8f10.7 12.7f13.4 12.6k9.0 228.0f506.7 144.6f590.0 264.7f283.4 226.7k530.0 1%.4f395.0 312.5f634.6 45.3 f 6 . 7 45.6k4.1 45.4k6.2 3.31k0.8 3.24k0.42 3.44k0.59 3.28f0.44 3.54f0.51 3.62f0.5 3.54f0.75 3.54f0.69 334f0.72 3.69 f0.85 3.6720.74 3.68k0.88
Numbers Age (years) Duration of arthritis (years) Rheumatoid Factor titre Age at menopause (years) Serum albumin (sit) Serum globulin (g/l) Erythrocyte Sedimentation Rate Haemaglobtn concentration (g/100 mi)
47.9k29.1
46.21t28.0
50.8k28.2
48.4f30.4
46.0530.1
49.2f30.7
13.8k1.8
13.9f1.8
13.6f1.9
12.lf1.7
12.4f 1.8
12.0f2.4
corticosteroid treated (CT) and non-corticosteroid treated (N-CT) groups, the male patients being significantly older than the female patients. There was no significant difference in age between the CT and N-CT male patients or between the C T and N-CT female patients. A similar pattern emerged when considering the duration of the arthritis which was, on average, present for longer in the male than in the female subjects. The mean titre of rheumatoid factor was higher in both the male and female C T groups than in the N-CT patients, though these differences did not reach statistical significance. In the female patients, the age of onset of the menopause was almost identical in the CTand N-CT groups. The mean serum albumin and globulin levels were slightly. but not significantly, higher in the male patients. The mean erythrocyte sedimentation rate was not significantly different in any of the groups.
The male patients had a significantly higher haemoglobin level than the female patients in all three groups. However, there was no significant difference between the C T and N-CT male patients and this was also true for the CT and N-CT female patients. Bone loss is well-known to occur in both male and female subjects with increasing age, as measured by the Femoral Index (7, 10). The femoral indices in the patient groups have therefore been compared by decades with the control subjects. In Fig. 1, the femoral indices of the noncorticosteroid treated fernale patient group is seen to be significantly lower than those of the control subjects in each decade between 25 and 74 years of age. In the female CT group, the femoral indices were significantly lower than in the normal subjects in all age groups, except in the decade 25 to 34 years of age (Fig. 2). When the
70
70
1
1
f
I
E
RMAlE
El
FEMORAL INDEX x)
,
0.001
P'D(DI
,
P~oo(11
,
PIwol
,
Paw!
,
I Normd
B
*A
25
0
25
35
45
55
65
n
AGE-)aon
Fig. I . The mean and Standard Error of the Femoral Index
are shown by decades in normal female subjects, and in female patients with RA. Scand J Rheumatologj 4
i5
15
if
65
A
AGE - m N
Fig. 2. The mean and Standard Error of the Femoral Index
are shown by decades in normal female subjects and in female patients with RA who have been treated with corticosteroids.
70
-
50-
FEMALE FEMORAL INDEX 3o
70
'
'
1 NS
NS
NS
NS
50
1
--
'
p
B
*
NS
NS
I
R.A.
I
NOtrnd
fl
R.A-Sl.roidTnhd
E
R*
I
femoral indices in the CT and N-CT groups were compared (Fig. 3), the C T groups at each decade had marginally lower mean values, but in no decade did this reach statistical significance. In the male patients who had not been treated with corticosteroids, the mean femoral indices were all lower than those of the control subjects in each decade between 25 and 74 years of age (Fig. 4), but only reached statistical significance between 45 and 64 years. The number of male patients who were treated with corticosteroids was small (twenty-four), one patient was below 45 years of age, and the rest ranged between 45 and 74 years of age. The mean values were lower in each of the three decades, compared with the control subjects, but only reached statistical significance in the 55 to 64 year age group (Fig. 5). When the CT male patients with RA were compared with the N-CT group in the three
0
1
I El
El
MALE FEMORAL INDEXJo
NS
0
Scand J Rheumatol Downloaded from informahealthcare.com by University of Auckland on 10/26/14 For personal use only.
-.
P
