URODYNAMICS
1
385 tified on an image analyser. There was a wide scatter in the amount of osteoid present, from 0’ 6% to 7 - 5% (osteoid volume as a percen- tage of total bone and marrow volume). The normal range in this laboratory for osteoid volume is up to 0 - 6%, and, although osteoid volume rises when the bone formation rate is high, the figures here are very high indeed. Much of the bone was woven bone, and the presence or absence of calcification fronts was difficult to determine in these cases. All fourteen patients were treated with calcitonin, with subjective relief of bone pain in ten. The four patients who did not respond to calcitonin had very high levels of osteoid (5 - 37%±2 - 01%) as com- pared with the ten responders (1 -84%±1 47%). Serum 2 OH cholecalciferol measurements were available for six patients. Values for three of the patients who responded to calcitonin were 9 - 0, 24 - 5, and 44 ng/ml, while values for three of the patients who did not respond to calcitonin were 4 - 0,4’ 2, and 6 - 2 ng/ml. The normal range is 3 - 0- 30, 0 0 ng/ml, so that the patients who did not respond to calcitonin not only had high levels of osteoid in affected bone, but also showed vitamin D levels at the lower end of the normal range. These four patients were treated with vitamin D (50 000 units daily for three patients, and 2 /-lg la-cholecalciferol/day for the fourth) with complete relief of bone pain within 3 weeks. In one of these pa- tients biopsy of bone free of Paget’s disease had also been done before the start of vitamin D therapy; this did not reveal osteomalacic changes. These observations lead us to suggest that areas of bone with a high bone formation rate may show osteomalacia when the vitamin D levels are in the lower part of the normal range, without generalis- ed osteomalacia. It is generally assumed that children, with a higher bone formation rate, have a greater requirement for vitamin D than adults, and it is reasonable to postulate that high vitamin D levels may be needed to sustain high rates of bone formation. The practical consequence of this observation is that relative vitamin D deficiency should be considered in the differential diagnosis of patients with Paget’s disease and severe bone pain. Vitamin D therapy is easier and cheaper than calcitonin treatment, and if there is any addi- tional reason to suspect relative D deficiency a therapeutic trial of vitamin D should be carried out. Localised osteomalacia in areas of bone with a high formation rate in patients with borderline low levels of vitamin D may not be con- fined to Paget’s disease. We suggest that a similar mechanism may occur in a minority of patients with severe bone pain from metastatic cancer, particularly elderly patients with a poor dietary intake. We thank the Middlesex Hospital Supraregional Laboratory for the 250H- vnamin-D assays. Department of Pathology, Welsh National School of Medicine, Cardiff CF4 4XN Department of Pathology, University Hospital of Wales Department of Rheumatology, East Glamorgan General Hospital E. D. WILLIAMS W. T. BARR K. T. RAJAN METABOLIC BONE DISEASE DURING PARENTERAL NUTRITION SiR,—There have recently been a number of reports of disorders of bone metabolism in infants 1,2 and adults3,4 receiving total parenteral nutrition (TPN). This syndrome is readily explicable in the neonate, where one problem lies in the provision of adequate calcium and phosphate in the small volume available. Moreover there is some uncertainty about the amount of vitamin D required and about the maturity of vitamin D hydroxylating enzyme systems, 1 Knight PJ, Buchanan S, Clatworthy HW Jr Calcium and phosphate requirements of preterm infants who require prolonged hyperalimentation. JAMA 1980; 243: 1244-46. 2. Klein GL, Cannon RA, Ament ME, et al. Rickets and osteopenia with normal 25-OH vitamin D in infants on parenteral nutrition Clin Res 1980; 28: 596A (abstr). 3. Shike M, Harrison JE, Sturtridge WC, et al Metabolic bone disease in patients receiv- ing long-term parenteral nutrition. Ann Intern Med 1980; 92: 343-50. 4 Klein GL, Ament ME, Bluestone R, et al Bone disease associated with total parenteral nutrition. Lancet 1980; ii. 1041-44. especially in preterm infants.5 Dr Klein and others have suggested 4 that the syndrome observed in adults may be unusual and difficult to explain because it was not characterised by abnormalities in blood biochemistry. We believe that this conclusion is misleading because they seem to have disregarded certain abnormal laboratory results which can be directly related to their parenteral nutrition regimen. We would not agree that the patients described4 had normal serum phosphate levels. 6 out of 11 patients had serum phosphate levels above the upper limit of normal (>1’45 mmol/1). Urinary phosphate excretion was also high in most patients. These obs’erva- tions are not surprising since Klein et al. provided 51 mmol phosphate daily (possibly plus unknown amounts from the aminoacid solution). With the moderate level of energy substrate and nitrogen provided, about 0 - 4 mmol phosphate/kg body weight should have been adequate, making a total of 15-25 mmol/day. We have found this sufficient in most subjects we have treated and have used 30 mmol phosphate per day only rarely and when glucose pro- vision has been high. We suggest that Klein et al. should not have dismissed the possibility that excess phosphate administration caused the bone disease in their patients. Klein et al. provided 1000 IU of vitamin D in their standard regimen. This is a high daily dose, expecially for ambulatory pa- tients. Serum 25 OH-vitamin D was reported as normal. In a recent study of patients receiving prolonged TPN3 Shike et al. reported a metabolic bone disease, characterised by high serum levels and ex- cessive urinary excretion of calcium and phosphate. These patients had received only 250 IU vitamin D daily. Total serum 25 OH- vitamin D was reported as normal or high, and examination of their vitamin D results shows that all but 3 of 16 had satisfactory 25 OH- vitamin D3 (endogenous, sunlight dependent) levels, but all 16 had raised 25 OH-vitamin D2 (exogenous) levels. Removal of vitamin D from the regimen promoted clinical and biochemical improvement. It appears that a distinction should be made between ambulatory pa- tients on TPN and those confined indoors and it may be that only the latter require supplementation with vitamin D. In these pa- tients, the amount of vitamin D necessary is likely to vary with clinical condition. Thus, there are several possible reasons for the development of metabolic bone disease in patients receiving TPN and it may not be necessary to postulate unknown factors. When bypassing the nor- mal regulatory mechanisms in skin for synthesis of vitamin D and in intestinal mucosa for calcium and phosphate absorption, the op- timum amount for intravenous administration must be carefully calculated. Guidance regarding the degree of supplementation should be sought from regular serum vitamin D analysis and from serum and urine mineral estimations. Biochemistry Department, Stobhill General Hospital, Glasgow G21 3UW Biochemistry Department, Glasgow Royal Infirmary B. F. ALLAM F. J. DRYBURGH A. SHENKIN URODYNAMICS SIR,-I endorse your comments on the role of urodynamics in the assessment of stress incontinence (Jan. 10, p. 82). But why, in your analysis of equipment costs, did you not refer to the place of simple cystometry (non-electronic and non-subtractant), at least for the reassurance of the many units not enjoying the expensive urodynamic equipment to which you exclusively refer? Simple cystometry permits the diagnosis of detrusor instability, and all you need is a container of saline connected to a catheter and standard central venous pressure apparatus via a three-way stopcock. Regional General Hospital, Dooradoyle, Limerick, Ireland DONAL O’SULLIVAN 5. Hillman LS, HaddadJG. Vitamin D metabolism and bone mineralization in premature and small-for-gestational-age infants. In: De Luca HF, Anast CS, eds Amsterdam. Pediatric diseases related to calcium. Elsevier/North Holland, 1980. 355-68 6. Shenkin A, Wretlind A Parenteral nutrition. World Rev Nutr Diet 1978, 28: 1-111
Transcript of URODYNAMICS
385
tified on an image analyser. There was a wide scatter in the amountof osteoid present, from 0’ 6% to 7 - 5% (osteoid volume as a percen-tage of total bone and marrow volume). The normal range in thislaboratory for osteoid volume is up to 0 - 6%, and, although osteoidvolume rises when the bone formation rate is high, the figures hereare very high indeed. Much of the bone was woven bone, and thepresence or absence of calcification fronts was difficult to determinein these cases.
All fourteen patients were treated with calcitonin, with subjectiverelief of bone pain in ten. The four patients who did not respond tocalcitonin had very high levels of osteoid (5 - 37%±2 - 01%) as com-pared with the ten responders (1 -84%±1 47%). Serum 2 OHcholecalciferol measurements were available for six patients. Valuesfor three of the patients who responded to calcitonin were 9 - 0,24 - 5, and 44 ng/ml, while values for three of the patients who didnot respond to calcitonin were 4 - 0,4’ 2, and 6 - 2 ng/ml. The normalrange is 3 - 0- 30, 0 0 ng/ml, so that the patients who did not respondto calcitonin not only had high levels of osteoid in affected bone, butalso showed vitamin D levels at the lower end of the normal range.These four patients were treated with vitamin D (50 000 units dailyfor three patients, and 2 /-lg la-cholecalciferol/day for the fourth)with complete relief of bone pain within 3 weeks. In one of these pa-tients biopsy of bone free of Paget’s disease had also been donebefore the start of vitamin D therapy; this did not revealosteomalacic changes.These observations lead us to suggest that areas of bone with a
high bone formation rate may show osteomalacia when the vitaminD levels are in the lower part of the normal range, without generalis-ed osteomalacia. It is generally assumed that children, with a higherbone formation rate, have a greater requirement for vitamin D thanadults, and it is reasonable to postulate that high vitamin D levelsmay be needed to sustain high rates of bone formation. The practicalconsequence of this observation is that relative vitamin D deficiencyshould be considered in the differential diagnosis of patients withPaget’s disease and severe bone pain. Vitamin D therapy is easierand cheaper than calcitonin treatment, and if there is any addi-tional reason to suspect relative D deficiency a therapeutic trial ofvitamin D should be carried out.Localised osteomalacia in areas of bone with a high formation rate
in patients with borderline low levels of vitamin D may not be con-fined to Paget’s disease. We suggest that a similar mechanism mayoccur in a minority of patients with severe bone pain from metastaticcancer, particularly elderly patients with a poor dietary intake.
We thank the Middlesex Hospital Supraregional Laboratory for the 250H-vnamin-D assays.
Department of Pathology,Welsh National School of Medicine,Cardiff CF4 4XN
Department of Pathology,University Hospital of Wales
Department of Rheumatology,East Glamorgan General Hospital
E. D. WILLIAMS
W. T. BARR
K. T. RAJAN
METABOLIC BONE DISEASE DURING PARENTERALNUTRITION
SiR,—There have recently been a number of reports of disordersof bone metabolism in infants 1,2 and adults3,4 receiving total
parenteral nutrition (TPN). This syndrome is readily explicable inthe neonate, where one problem lies in the provision of adequatecalcium and phosphate in the small volume available. Moreoverthere is some uncertainty about the amount of vitamin D requiredand about the maturity of vitamin D hydroxylating enzyme systems,
1 Knight PJ, Buchanan S, Clatworthy HW Jr Calcium and phosphate requirements ofpreterm infants who require prolonged hyperalimentation. JAMA 1980; 243:1244-46.
2. Klein GL, Cannon RA, Ament ME, et al. Rickets and osteopenia with normal 25-OHvitamin D in infants on parenteral nutrition Clin Res 1980; 28: 596A (abstr).
3. Shike M, Harrison JE, Sturtridge WC, et al Metabolic bone disease in patients receiv-ing long-term parenteral nutrition. Ann Intern Med 1980; 92: 343-50.
4 Klein GL, Ament ME, Bluestone R, et al Bone disease associated with total parenteralnutrition. Lancet 1980; ii. 1041-44.
especially in preterm infants.5 Dr Klein and others have suggested 4that the syndrome observed in adults may be unusual and difficult toexplain because it was not characterised by abnormalities in bloodbiochemistry. We believe that this conclusion is misleading becausethey seem to have disregarded certain abnormal laboratory resultswhich can be directly related to their parenteral nutrition regimen.We would not agree that the patients described4 had normal
serum phosphate levels. 6 out of 11 patients had serum phosphatelevels above the upper limit of normal (>1’45 mmol/1). Urinaryphosphate excretion was also high in most patients. These obs’erva-tions are not surprising since Klein et al. provided 51 mmolphosphate daily (possibly plus unknown amounts from theaminoacid solution). With the moderate level of energy substrateand nitrogen provided, about 0 - 4 mmol phosphate/kg body weightshould have been adequate, making a total of 15-25 mmol/day. Wehave found this sufficient in most subjects we have treated and haveused 30 mmol phosphate per day only rarely and when glucose pro-vision has been high. We suggest that Klein et al. should not havedismissed the possibility that excess phosphate administrationcaused the bone disease in their patients.Klein et al. provided 1000 IU of vitamin D in their standard
regimen. This is a high daily dose, expecially for ambulatory pa-tients. Serum 25 OH-vitamin D was reported as normal. In a recentstudy of patients receiving prolonged TPN3 Shike et al. reported ametabolic bone disease, characterised by high serum levels and ex-cessive urinary excretion of calcium and phosphate. These patientshad received only 250 IU vitamin D daily. Total serum 25 OH-vitamin D was reported as normal or high, and examination of theirvitamin D results shows that all but 3 of 16 had satisfactory 25 OH-vitamin D3 (endogenous, sunlight dependent) levels, but all 16 hadraised 25 OH-vitamin D2 (exogenous) levels. Removal of vitamin Dfrom the regimen promoted clinical and biochemical improvement.It appears that a distinction should be made between ambulatory pa-tients on TPN and those confined indoors and it may be that onlythe latter require supplementation with vitamin D. In these pa-tients, the amount of vitamin D necessary is likely to vary withclinical condition.
Thus, there are several possible reasons for the development ofmetabolic bone disease in patients receiving TPN and it may not benecessary to postulate unknown factors. When bypassing the nor-mal regulatory mechanisms in skin for synthesis of vitamin D and inintestinal mucosa for calcium and phosphate absorption, the op-timum amount for intravenous administration must be carefullycalculated. Guidance regarding the degree of supplementationshould be sought from regular serum vitamin D analysis and fromserum and urine mineral estimations.
Biochemistry Department,Stobhill General Hospital,Glasgow G21 3UW
Biochemistry Department,Glasgow Royal Infirmary
B. F. ALLAM
F. J. DRYBURGHA. SHENKIN
URODYNAMICS
SIR,-I endorse your comments on the role of urodynamics in theassessment of stress incontinence (Jan. 10, p. 82). But why, in youranalysis of equipment costs, did you not refer to the place of simplecystometry (non-electronic and non-subtractant), at least for thereassurance of the many units not enjoying the expensiveurodynamic equipment to which you exclusively refer? Simplecystometry permits the diagnosis of detrusor instability, and all youneed is a container of saline connected to a catheter and standardcentral venous pressure apparatus via a three-way stopcock.
Regional General Hospital,Dooradoyle, Limerick, Ireland DONAL O’SULLIVAN
5. Hillman LS, HaddadJG. Vitamin D metabolism and bone mineralization in prematureand small-for-gestational-age infants. In: De Luca HF, Anast CS, eds Amsterdam.Pediatric diseases related to calcium. Elsevier/North Holland, 1980. 355-68
6. Shenkin A, Wretlind A Parenteral nutrition. World Rev Nutr Diet 1978, 28: 1-111
