Age and Ageing (1976), 5, 119
THE CAUSES OF OSTEOMALACIA IN THE ELDERLY S. G. P. WEBSTER*, J. T. LEEMING AND E. M. WILKINSON
Department of Geriatrics, University Hospital of South Manchester, Nell Lane, Manchester M20 8LR Summary Investigations into the causes of osteomalacia in 12 geriatric patients with a histologically proven diagnosis, revealed no predominant aetiology. The metabolic bone disease in these patients appeared to have multifactorial causes in at least half the cases. INTRODUCTION
Nobody is certain of the frequency of osteomalacia in the elderly members of our population. Anderson et al. (1966) found an incidence of 4% amongst 100 consecutive admissions to a Glasgow geriatric unit. This is, however, a special group sufficiently ill or dependent to require admission to hospital. Hodkinson (1971) investigated 35 elderly patients who had sustained a fractured neck of femur—a group where osteomalacia might have been expected to be high—but he found no histologically proven cases. Even when osteomalacia has been definitely confirmed histologically, there are often considerable difficulties in deciding upon the cause for the vitamin D deficiency which has led to the bone changes. Chalmers (1968) described 93 cases of osteomalacia, but was unable to find a primary cause in 34. Chalmers patients included people of all ages, but it was amongst the 50 subjects older than 70 years where the highest number of cases without causes was found. The uncertainty in old age is not surprising as the necessary information is often not available and intensive investigation neither justified or possible. However, the aim of the present paper is to assess the various aetiological factors in 12 cases of histologically proven osteomalacia found in patients attending or admitted to a busy geriatric unit. Unfortunately, much of the information is unavoidably incomplete but some conclusions are suggested as to the significance of the various causes of osteomalacia in old age. Patients and Methods All 12 patients included in this study were diagnosed to have osteomalacia on the basis of the presence of continuous wide osteoid seams demonstrated in bone biopsies. The specimens of bone were removed from the patients iliac crest under local anaesthesia using a Blackburn's 0.5 cm trephine. Undecalcified sections were prepared and stained by the Von Kossa technique. Only two patients were men and ten were female. Their ages ranged from 73 to 94 years (mean 83 years). • Present address: Chesterton Hospital, Cambridge.
S. G. P. Webster, J. T. Leeming and E. M. Wilkinson
120
A seven-day recall dietary history was obtained infivecases, either from the patient or from a relative or friend closely involved with the patient's care before admission to hospital. On the basis of the information obtained, the mean daily intake of vitamin D was estimated using the tables of McCance & Widdowson (I960). Both oral and intravenous xylose tests were performed in all patients, 25 g of D-xylose being given by mouth (except two patients who received a 5 g dose) and 5 g being given intravenously, both after at least eight hours fast. A five-hour urine was collected after each administration. Using the method of Kendal (1970), a ratio from the results of both tests was used to assess small-bowel function. The amount of xylose passed in the urine in five hours after intravenous test was used as an assessment of renal function. Proximal jejunal biopsies were obtained in seven patients using the double-tube technique of Evans et al. (1970). The dissecting microscope appearances of the specimens were categorized according to the predominant villous form. Group I Group II Group III Group IV
fingers narrow leaves broad leaves or ridges convolutions
A history of being housebound was also sought and any period greater than two years considered significant. RESULTS
See Table I. Table I. Factors involved in the aetiology of osteomalacia in 12 elderly patients Sex M F F M F F F F F F F F
Age
Renal function
91 70 81 84 86 81 89 94 88 84 78 73
0.2 1.0 0.9 0.8 0.5 1.0 1.6 2.0 1.7 2.8 1.0 0.9
Normal values
>1.0
Jejunal vtili 1 — 1 2 3 —
2 —• — 1 4 lor 2
Dietary Vit. D — —
Good Good — Low — PLowf
Good — — Low
Good: >70iu
Small-bowel function
House-bound
>2 years
Subnormal* 2.4 2.4 2.2 1.4 3.8 0.9 2.2 2.5 1.9
Normal* 2.1
—
+ — + — — + + + —
>1.8
• Slightly different method with 5 g oral dose used, f Dietary history not taken by a trained dietitian. DISCUSSION OF RESULTS
Although there is some doubt as to the exact daily requirement of vitamin D, a minimum level of 70 iu is most frequently accepted. Dent & Smith (1969) stated that an intake below this level would result in nutritional osteomalacia. Of the five patients in the present series where an accurate dietary history was obtained, only two had levels of less than 70 iu daily. In a third case, it was also suspected that intake was extremely
The Causes of Osteomalacia in the Elderly
121
poor, but reliable details could not be obtained. Three patients definitely had adequate intakes—the remaining six were investigated before the services of an experienced dietitian were available to the unit, and authoritative assessments could not be made. What is more disturbing than the lack of evidence of dietary deficiency in at least half of our patients with osteomalacia is that patients with bones apparently free of osteomalacia are taking an equally poor diet. In a survey of 104 patients and old people admitted to the University Hospital of South Manchester, or living in its' neighbourhood, 41 were taking less than 70 iu of vitamin D daily (Wilkinson et al. 1974). Other surveys (Macleod 1970, Lonergan 1971) have also found a very high incidence of low vitamin D intakes—certainly greatly in excess of the apparent frequency of osteomalacia in the elderly section of the population. One must therefore have serious doubts as to the accuracy of the estimated minimum requirement. In the seven patients in which it was possible to make an examination of the jejunal mucosa, the villi could only be considered to show an abnormal pattern in two cases (those classified as being in Groups III and IV). However, a similar degree of abnormality was seen in a larger group (39 patients) of equivalent age with no evidence of osteomalacia (Webster & Leeming 1975a). Amongst the 39 patients, 20% were classified as being Group III or IV compared with 28% from those with proven osteomalacia. Small-bowel function as indicated by the xylose tolerance test ratio, was similarly no more impaired amongst the group with osteomalacia than found in a random group of geriatric inpatients. The normal range for the test (mean ± 2 s.D.) was calculated as 1.8 to 4.8 from results obtained in 20 young subjects aged 18 to 35 years. Of 85 geriatric patients 26% were found to give results below this normal range (Webster & Leeming 19756). In comparison, 25% of the patients with osteomalacia had subnormal results. Therefore, dietary intake of vitamin D, and small-bowel structure or function cannot be shown to be worse in geriatric patients with osteomalacia than in routine geriatric admissions. Using the five-hour urinary excretion of xylose after an intravenous dose of 5 g as an indicator of renal function, there does appear to be a difference between those geriatric patients with definite osteomalacia and randomly chosen patients. The normal range for urinary recovery calculated as the mean ± 2 s.D. from results obtained in 23 young healthy subjects aged 18 to 35 years, was 1.4 to 3.0 g (Webster & Leeming 19756). Seventy-five per cent of geriatric patients with osteomalacia are below this range, whereas only 21% of geriatric patients without evidence of osteomalacia have results below the lower limit of normal. An incidence of being housebound for two years or more in five subjects (42%) was double the finding in another group of 33 patients who had negative bone biopsies. The frequency of being housebound in the second group, 21%, compares well with Townsend & Wedderburn's (1965) report of 20% of the over-65-year-old population being similarly disabled. CONCLUSION
Because the number of patients with osteomalacia is small and the information available incomplete, it is not possible to demonstrate statistically significant differences between them and geriatric patients without evidence of metabolic bone disease. However, the above results do suggest that the cause of osteomalacia in elderly people is often multi-
122
S. G. P. Webster, J. T. Leeming and E. M. Wilkinson
factorial. In addition, it would appear that renal function in the osteomalacia group is more frequently impaired than in other subjects of similar age. As it is now known that the kidney performs an essential function in making vitamin D biologically active, perhaps more attention should be paid to this mechanism as possibly the most significant causative factor in the elderly. The poor response of elderly patients with osteomalacia to intravenous doses of vitamin D3 as shown by Webster et al. (1975) is also suggestive of impaired metabolism of the substance. The higher incidence of being housebound found in the osteomalacia patients may also be a significant causative factor. It should, however, be remembered that the limitation of mobility may in fact be secondary to the bone disorder. ACKNOWLEDGEMENTS
During the completion of this work S.G.P.W. was in receipt of a grant from the Manchester Regional Hospital Board and E.M.W. a grant from the British Nutrition Foundation. REFERENCES
I., CAMPBELL, A. E. R., DUNN, A. & RUNCIMAN, J. B. M. (1966) Osteomalacia in elderly women. Scot. Med. J. 11, 429—35. CHALMERS, J. (1968) Osteomalacia: a review of 93 cases. J. R. Coll. Surg. Edinb. 13, 255-75. DENT, C. E. & SMITH, R. (1969) Nutritional osteomalacia. Q. J. Med. 38, 195-209. EVANS, N., FARROW, L. J., HARDING, A. & STEWART, J. S. (1970) New techniques for speeding small intestinal biopsy. Out 11, 88—9. HODKINSON, H. M. (1971) Fracture of the femoral neck in the elderly. Assessment of the role of osteomalacia. Gerontol. Clin. 13, 153-8. KENDALL, M. J. (1970) The influence of age on the xylose absorption test. Gut 11, 498-501. LONERGAN, M. N. (1971) Nutritional survey of the elderly. Nutrition 25, 30-36. MCCANCE, R. A. & WiDDOWSON, E. M. (1960) The composition of foods. Spec. Rep. Ser. Med. Res. Counc. (Lond.) No. 297. London: H.M.S.O. MACLEOD, C. C. (1970) Dietary intake of older people. Nutrition 24, 24-29. TOWNSEND, P. & WEDDERBURN, D. (1965) The Aged in the Welfare State London: Bell. WEBSTER, S. G. P. & LEEMING, J. T. (1975a) The appearance of the small bowel mucosa in old age. Age & Ageing 4, 168-74. WEBSTER, S. G. P. & LEEMING, J. T. (19756) Assessment of small bowel function in the elderly using a modified xylose tolerance test. Gut. 16, 109-113. WEBSTER, S. G. P., LEEMING, J. T., WHITTAKER, J. S. & WILKINSON, M. (1975) An evaluation of the intravenous vitamin D test in geriatric patients with suspected osteomalacia. Age £f Ageing 4, 69-72. WILKINSON, E. M., LEEMING, J. T., WEBSTER, S. G. P. (1974) Intakes and sources of vitamin D in a group of patients in the South Manchester area. Nutrition 28, 398—402. ANDERSON,
THE CAUSES OF OSTEOMALACIA IN THE ELDERLY S. G. P. WEBSTER*, J. T. LEEMING AND E. M. WILKINSON
Department of Geriatrics, University Hospital of South Manchester, Nell Lane, Manchester M20 8LR Summary Investigations into the causes of osteomalacia in 12 geriatric patients with a histologically proven diagnosis, revealed no predominant aetiology. The metabolic bone disease in these patients appeared to have multifactorial causes in at least half the cases. INTRODUCTION
Nobody is certain of the frequency of osteomalacia in the elderly members of our population. Anderson et al. (1966) found an incidence of 4% amongst 100 consecutive admissions to a Glasgow geriatric unit. This is, however, a special group sufficiently ill or dependent to require admission to hospital. Hodkinson (1971) investigated 35 elderly patients who had sustained a fractured neck of femur—a group where osteomalacia might have been expected to be high—but he found no histologically proven cases. Even when osteomalacia has been definitely confirmed histologically, there are often considerable difficulties in deciding upon the cause for the vitamin D deficiency which has led to the bone changes. Chalmers (1968) described 93 cases of osteomalacia, but was unable to find a primary cause in 34. Chalmers patients included people of all ages, but it was amongst the 50 subjects older than 70 years where the highest number of cases without causes was found. The uncertainty in old age is not surprising as the necessary information is often not available and intensive investigation neither justified or possible. However, the aim of the present paper is to assess the various aetiological factors in 12 cases of histologically proven osteomalacia found in patients attending or admitted to a busy geriatric unit. Unfortunately, much of the information is unavoidably incomplete but some conclusions are suggested as to the significance of the various causes of osteomalacia in old age. Patients and Methods All 12 patients included in this study were diagnosed to have osteomalacia on the basis of the presence of continuous wide osteoid seams demonstrated in bone biopsies. The specimens of bone were removed from the patients iliac crest under local anaesthesia using a Blackburn's 0.5 cm trephine. Undecalcified sections were prepared and stained by the Von Kossa technique. Only two patients were men and ten were female. Their ages ranged from 73 to 94 years (mean 83 years). • Present address: Chesterton Hospital, Cambridge.
S. G. P. Webster, J. T. Leeming and E. M. Wilkinson
120
A seven-day recall dietary history was obtained infivecases, either from the patient or from a relative or friend closely involved with the patient's care before admission to hospital. On the basis of the information obtained, the mean daily intake of vitamin D was estimated using the tables of McCance & Widdowson (I960). Both oral and intravenous xylose tests were performed in all patients, 25 g of D-xylose being given by mouth (except two patients who received a 5 g dose) and 5 g being given intravenously, both after at least eight hours fast. A five-hour urine was collected after each administration. Using the method of Kendal (1970), a ratio from the results of both tests was used to assess small-bowel function. The amount of xylose passed in the urine in five hours after intravenous test was used as an assessment of renal function. Proximal jejunal biopsies were obtained in seven patients using the double-tube technique of Evans et al. (1970). The dissecting microscope appearances of the specimens were categorized according to the predominant villous form. Group I Group II Group III Group IV
fingers narrow leaves broad leaves or ridges convolutions
A history of being housebound was also sought and any period greater than two years considered significant. RESULTS
See Table I. Table I. Factors involved in the aetiology of osteomalacia in 12 elderly patients Sex M F F M F F F F F F F F
Age
Renal function
91 70 81 84 86 81 89 94 88 84 78 73
0.2 1.0 0.9 0.8 0.5 1.0 1.6 2.0 1.7 2.8 1.0 0.9
Normal values
>1.0
Jejunal vtili 1 — 1 2 3 —
2 —• — 1 4 lor 2
Dietary Vit. D — —
Good Good — Low — PLowf
Good — — Low
Good: >70iu
Small-bowel function
House-bound
>2 years
Subnormal* 2.4 2.4 2.2 1.4 3.8 0.9 2.2 2.5 1.9
Normal* 2.1
—
+ — + — — + + + —
>1.8
• Slightly different method with 5 g oral dose used, f Dietary history not taken by a trained dietitian. DISCUSSION OF RESULTS
Although there is some doubt as to the exact daily requirement of vitamin D, a minimum level of 70 iu is most frequently accepted. Dent & Smith (1969) stated that an intake below this level would result in nutritional osteomalacia. Of the five patients in the present series where an accurate dietary history was obtained, only two had levels of less than 70 iu daily. In a third case, it was also suspected that intake was extremely
The Causes of Osteomalacia in the Elderly
121
poor, but reliable details could not be obtained. Three patients definitely had adequate intakes—the remaining six were investigated before the services of an experienced dietitian were available to the unit, and authoritative assessments could not be made. What is more disturbing than the lack of evidence of dietary deficiency in at least half of our patients with osteomalacia is that patients with bones apparently free of osteomalacia are taking an equally poor diet. In a survey of 104 patients and old people admitted to the University Hospital of South Manchester, or living in its' neighbourhood, 41 were taking less than 70 iu of vitamin D daily (Wilkinson et al. 1974). Other surveys (Macleod 1970, Lonergan 1971) have also found a very high incidence of low vitamin D intakes—certainly greatly in excess of the apparent frequency of osteomalacia in the elderly section of the population. One must therefore have serious doubts as to the accuracy of the estimated minimum requirement. In the seven patients in which it was possible to make an examination of the jejunal mucosa, the villi could only be considered to show an abnormal pattern in two cases (those classified as being in Groups III and IV). However, a similar degree of abnormality was seen in a larger group (39 patients) of equivalent age with no evidence of osteomalacia (Webster & Leeming 1975a). Amongst the 39 patients, 20% were classified as being Group III or IV compared with 28% from those with proven osteomalacia. Small-bowel function as indicated by the xylose tolerance test ratio, was similarly no more impaired amongst the group with osteomalacia than found in a random group of geriatric inpatients. The normal range for the test (mean ± 2 s.D.) was calculated as 1.8 to 4.8 from results obtained in 20 young subjects aged 18 to 35 years. Of 85 geriatric patients 26% were found to give results below this normal range (Webster & Leeming 19756). In comparison, 25% of the patients with osteomalacia had subnormal results. Therefore, dietary intake of vitamin D, and small-bowel structure or function cannot be shown to be worse in geriatric patients with osteomalacia than in routine geriatric admissions. Using the five-hour urinary excretion of xylose after an intravenous dose of 5 g as an indicator of renal function, there does appear to be a difference between those geriatric patients with definite osteomalacia and randomly chosen patients. The normal range for urinary recovery calculated as the mean ± 2 s.D. from results obtained in 23 young healthy subjects aged 18 to 35 years, was 1.4 to 3.0 g (Webster & Leeming 19756). Seventy-five per cent of geriatric patients with osteomalacia are below this range, whereas only 21% of geriatric patients without evidence of osteomalacia have results below the lower limit of normal. An incidence of being housebound for two years or more in five subjects (42%) was double the finding in another group of 33 patients who had negative bone biopsies. The frequency of being housebound in the second group, 21%, compares well with Townsend & Wedderburn's (1965) report of 20% of the over-65-year-old population being similarly disabled. CONCLUSION
Because the number of patients with osteomalacia is small and the information available incomplete, it is not possible to demonstrate statistically significant differences between them and geriatric patients without evidence of metabolic bone disease. However, the above results do suggest that the cause of osteomalacia in elderly people is often multi-
122
S. G. P. Webster, J. T. Leeming and E. M. Wilkinson
factorial. In addition, it would appear that renal function in the osteomalacia group is more frequently impaired than in other subjects of similar age. As it is now known that the kidney performs an essential function in making vitamin D biologically active, perhaps more attention should be paid to this mechanism as possibly the most significant causative factor in the elderly. The poor response of elderly patients with osteomalacia to intravenous doses of vitamin D3 as shown by Webster et al. (1975) is also suggestive of impaired metabolism of the substance. The higher incidence of being housebound found in the osteomalacia patients may also be a significant causative factor. It should, however, be remembered that the limitation of mobility may in fact be secondary to the bone disorder. ACKNOWLEDGEMENTS
During the completion of this work S.G.P.W. was in receipt of a grant from the Manchester Regional Hospital Board and E.M.W. a grant from the British Nutrition Foundation. REFERENCES
I., CAMPBELL, A. E. R., DUNN, A. & RUNCIMAN, J. B. M. (1966) Osteomalacia in elderly women. Scot. Med. J. 11, 429—35. CHALMERS, J. (1968) Osteomalacia: a review of 93 cases. J. R. Coll. Surg. Edinb. 13, 255-75. DENT, C. E. & SMITH, R. (1969) Nutritional osteomalacia. Q. J. Med. 38, 195-209. EVANS, N., FARROW, L. J., HARDING, A. & STEWART, J. S. (1970) New techniques for speeding small intestinal biopsy. Out 11, 88—9. HODKINSON, H. M. (1971) Fracture of the femoral neck in the elderly. Assessment of the role of osteomalacia. Gerontol. Clin. 13, 153-8. KENDALL, M. J. (1970) The influence of age on the xylose absorption test. Gut 11, 498-501. LONERGAN, M. N. (1971) Nutritional survey of the elderly. Nutrition 25, 30-36. MCCANCE, R. A. & WiDDOWSON, E. M. (1960) The composition of foods. Spec. Rep. Ser. Med. Res. Counc. (Lond.) No. 297. London: H.M.S.O. MACLEOD, C. C. (1970) Dietary intake of older people. Nutrition 24, 24-29. TOWNSEND, P. & WEDDERBURN, D. (1965) The Aged in the Welfare State London: Bell. WEBSTER, S. G. P. & LEEMING, J. T. (1975a) The appearance of the small bowel mucosa in old age. Age & Ageing 4, 168-74. WEBSTER, S. G. P. & LEEMING, J. T. (19756) Assessment of small bowel function in the elderly using a modified xylose tolerance test. Gut. 16, 109-113. WEBSTER, S. G. P., LEEMING, J. T., WHITTAKER, J. S. & WILKINSON, M. (1975) An evaluation of the intravenous vitamin D test in geriatric patients with suspected osteomalacia. Age £f Ageing 4, 69-72. WILKINSON, E. M., LEEMING, J. T., WEBSTER, S. G. P. (1974) Intakes and sources of vitamin D in a group of patients in the South Manchester area. Nutrition 28, 398—402. ANDERSON,
